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Maurizio Muscaritoli

Publications and source records attributed to Maurizio Muscaritoli.

At least 19 recordsLinked to original sources
PubMed2006

Skeletal muscle apoptosis is not increased in gastric cancer patients with mild-moderate weight loss.

Numerous experimental and clinical studies have shown that skeletal muscle apoptotis may increase in wasting conditions and suggest that apoptosis might contribute to the loss of lean body mass. Data in cancer patients are still lacking. The present study aimed at verifying whether apoptosis was enhanced in the skeletal muscle of 16 patients with gastric cancer with respect to controls. A biopsy specimen was obtained from the rectus abdominis muscle. The occurrence of apoptosis in muscle biopsies was determined morphologically by the fluorescent transferase-mediated dUTP nick end labeling assay and by immunohistochemistry for caspase-3 and caspase-1. Mean weight loss was 6+/-2% in cancer patients and 0.5+/-0.1% in controls (p<0.0001). Serum albumin levels (g/dL) were 3.7+/-0.3 in cancer patients and 4.1+/-0.2 in controls (p<0.05). The percentage of apoptotic myonuclei was similar in cancer patients and in controls (1.5+/-0.3 versus 1.4+/-0.2, respectively; p=ns), in gastric cancer patients with mild (1.6+/-0.4) or moderate-severe weight loss (1.4+/-0.5) (p=ns), and in the different stages of disease (stages I-II: 1.5+/-0.7; stage III: 1.3+/-0.4; stage IV: 1.6+/-0.3; p=ns). By immunohistochemistry, caspase-1 and caspase-3 positive fibers were absent in controls and in neoplastic patients. Poly-ADP-ribosyl polymerase, a typical caspase-3 substrate whose processing is indicative of caspase-3 activation, was not cleaved in muscle biopsies of cancer patients. These data suggest that skeletal muscle apoptosis is not increased in neoplastic patients with mild-moderate weight loss and argue against the hypotheses that caspase-3 activation might be an essential step of myofibrillar proteolysis in cancer-related muscle wasting.

Adult↗
PubMed2006

IGF-1 is downregulated in experimental cancer cachexia.

Cancer cachexia is characterized by skeletal muscle wasting that is mainly supported by hypercatabolism. Muscle atrophy has been suggested to depend on impaired IGF-1 signal transduction pathway. The present study has been aimed at investigating the IGF-1 system in rats bearing the AH-130 hepatoma, a well-characterized model of cachexia. IGF-1 mRNA expression in the gastrocnemius of tumor hosts progressively decreases to approximately 50% of controls. By contrast, both IGF-1 receptor and insulin receptor mRNA levels increase in day 7 AH-130 hosts. IGF-1 and insulin circulating levels, as well as IGF-1 expression in the liver, are reduced. Muscle wasting in the AH-130 bearers is associated with hyperactivation of the ubiquitin-proteasome system. Consistently, the mRNA levels of ubiquitin and of the ubiquitin ligases atrogin-1 and MuRF1 are significantly increased in the gastrocnemius of day 7 AH-130 hosts. Exogenous IGF-1 administered to tumor bearers does not prevent cachexia. IGF-1 mRNA levels also have been evaluated in the gastrocnemius of AH-130 hosts treated with pentoxifylline, an inhibitor of TNF-alpha synthesis, alone or combined with formoterol, a beta(2)-adrenergic agonist. Both treatments partially correct muscle atrophy without modifying IGF-1 and atrogin-1 mRNA levels, whereas MuRF1 hyperexpression is reduced by the combination of pentoxifylline with formoterol. These results demonstrate for the first time that the IGF-1 system is downregulated in cancer cachexia, although the underlying mechanism remains unknown. Moreover, no simple relation linking IGF-1 and/or atrogin-1 mRNA levels and muscle atrophy could be observed in these experimental conditions. Further studies are thus needed to clarify both issues.

Adrenergic beta-Agonists↗
PubMed2006

Antimyopathic effects of carnitine and nicotine.

PURPOSE OF REVIEW: The clinical course of most chronic diseases is associated with declined energy intake and nutrient-resistant progressive myopathy, characterized by accelerated proteolysis and impaired function. This anorexia/cachexia syndrome leads to deterioration of quality of life, and increased morbidity and mortality. The clinical efficacy of currently available therapeutic strategies is limited and more effective treatments are needed. RECENT FINDINGS: Chronic systemic inflammation, triggered and sustained by cytokines, and increased oxidative stress contribute to the pathogenesis of the anorexia/cachexia syndrome. Carnitine and nicotine have recently been tested as immunomodulating and antioxidant agents. In particular, carnitine supplementation has been shown to reduce chronic inflammation and oxidative stress in hemodialysis patients and, in cancer patients, yielding to reduced fatigue and improved outcome. Nicotine is able to induce the anti-inflammatory activity of the vagus nerve. In animal models of sepsis and cancer, the nicotine-induced supplementation resulted in better protection of nutritional status and improved survival. SUMMARY: In the continuous effort to develop more efficacious strategies against the anorexia/cachexia syndrome, carnitine and nicotine may represent a further therapeutic tool. More clinical studies are needed, however, before their use can be routinely suggested.

Animals↗
PubMed2005

Prevention and treatment of cancer cachexia: new insights into an old problem.

Cancer cachexia (CC) is a multifactorial paraneoplastic syndrome characterized by anorexia, body weight loss, loss of adipose tissue and skeletal muscle, accounting for at least 20% of deaths in neoplastic patients. CC significantly impairs quality of life and response to anti-neoplastic therapies, increasing morbidity and mortality of cancer patients. Muscle wasting is the most important phenotypic feature of CC and the principal cause of function impairment, fatigue and respiratory complications, mainly related to a hyperactivation of muscle proteolytic pathways. Most therapeutic strategies to CC have proven to be only partially effective . The inhibition of catabolic processes in muscle has been attempted pharmacologically with encouraging results in animal models. However, data in the clinical setting are still scanty and contradictory. Stimulation of muscle anabolism could represent a promising and valid therapeutic alternative for cancer-related muscle wasting. This goal may be currently achieved with the conventional, short-acting and adverse side effect-rich anabolic steroids. Insulin-like growth factor-1 (IGF-1) plays a critical role in muscle homeostasis, hypertrophy and regeneration. IGF-1 overexpression at the muscular level by gene therapy reverses muscle hypotrophy secondary to catabolic conditions and induces muscle hypertrophy increasing muscle mass and strength. This allows the speculation that this approach could also prove effective in modulating cancer-induced muscle wasting, while avoiding the potentially hazardous side effects of systemic IGF-1 administration. The present review will focus on the potential biochemical and molecular targets of CC therapy, and will define the rationale for a novel, gene therapy-based approach.

Cachexia↗
PubMed2005

Therapy insight: Cancer anorexia-cachexia syndrome--when all you can eat is yourself.

Tumor growth is associated with profound metabolic and neurochemical alterations, which can lead to the onset of anorexia-cachexia syndrome. Anorexia is defined as the loss of the desire to eat, while cachexia results from progressive wasting of skeletal muscle mass--and to a lesser extent adipose tissue--occurring even before weight loss becomes apparent. Cancer anorexia-cachexia syndrome is highly prevalent among cancer patients, has a large impact on morbidity and mortality, and impinges on patient quality of life. However, its clinical relevance is frequently overlooked, and treatments are usually only attempted during advanced stages of the disease. The pathogenic mechanisms of cachexia and anorexia are multifactorial, but cytokines and tumor-derived factors have a significant role, thereby representing a suitable therapeutic target. Energy expenditure in anorexia is frequently increased while energy intake is decreased, which further exacerbates the progressive deterioration of nutritional status. The optimal therapeutic approach to anorectic-cachectic cancer patients should be based on both changes in dietary habits, achieved via nutritional counseling; and drug therapy, aimed at interfering with cytokine expression or activity. Our improved understanding of the influence a tumor has on the host's metabolism is advancing new therapeutic approaches, which are likely to result in better preservation of nutritional status if started concurrently with specific antineoplastic treatment.

Anorexia↗
PubMed2005

Malnutrition in hemodialysis patients: what therapy?

Malnutrition is common in hemodialysis patients and is a powerful predictor of morbidity and mortality. Although much progress has been made in recent years in identifying the causes and pathogenesis of malnutrition in hemodialysis patients, as well as recognizing the link between malnutrition and morbidity and mortality, no consensus has been reached concerning its management. Along with such conventional interventions as nutritional counseling, oral nutritional supplements, and intradialytic parenteral nutrition, novel preventive and therapeutic strategies have been tested, such as appetite stimulants, growth hormone, androgenic anabolic steroids, and anti-inflammatory drugs, with contradictory and nonconclusive results. Malnutrition still remains a great challenge for nephrologists in the third millennium.

Acidosis↗
PubMed2005

Variables associated with reduced dietary intake in hemodialysis patients.

BACKGROUND: Among the causes of malnutrition in hemodialysis (HD) patients, inadequate dietary intake (IDI) seems to be one of the most frequent and important. Although it has been hypothesized that IDI might be secondary to uremia, anorexia, underlying illness, psychosocial conditions, loss of dentures, depression, aging, or chronic inflammation, definite data on the etiology of IDI in HD patients are still lacking. The goal of this study was to measure the actual dietary energy and protein intakes in stable HD patients and to evaluate which demographic, clinical, dialytic, and humoral variables were associated with a dietary intake lower than recommended by international guidelines. METHODS: Thirty-seven patients maintained on regular HD, 3 times per week for 4 hours per session, were included in the study. In addition to epidemiologic data, patients were scrutinized for dry weight, weight change in the last 6 months, height, Body Mass Index, Kt/V, serum leptin, leptin-BMI ratio, presence of anorexia, and dietary energy and protein intake. Anorexia was assessed by means of a questionnaire in which the presence of major symptoms, namely meat aversion, taste and smell alterations, nausea and/or vomiting, and early satiety, was investigated. Dietary intake was recorded for 3 days after questionnaire administration by means of 3-day diet diaries. RESULTS: Overall, the mean (+/- standard deviation) dietary energy and protein intakes were 24.9 +/- 10.1 kcal/kg/day and 0.64 +/- 0.4 g protein/kg/day, respectively. Twenty-six patients (70.2%) had energy and protein intakes lower than recommended, 7 (18.9%) had adequate energy intake but inadequate protein intake, 1 (2.7%) had adequate protein intake and inadequate energy intake, and 3 (8.1%) had both adequate energy and adequate protein intakes. Anorexia was present in 14 of the 26 (53%) patients with low protein and energy intakes, and was absent in the other groups ( P =.003). The age of patients with inadequate energy and protein intakes was significantly higher than the age of patients with adequate energy and protein intakes (62.1 +/- 10.4 versus 37 +/- 20.8, P <.001) and the age of patients with only adequate energy intake (40.5 +/- 10.4, P <.001). Twenty-seven patients (73%) had an energy intake <30 kcal/kg/day, and 10 (27%) had an energy intake > or =30 kcal/kg/day. Compared with patients with energy intakes > or =30 kcal/kg/day, patients with energy intakes <30 kcal/kg/day were significantly older ( P =.0001) and more frequently were anorexic (P <.05). Compared with patients with protein intakes > or =1.2 g/kg/day, patients with protein intakes <1.2 g/kg/day were significantly older (P <.001). Limiting the analysis to the 33 patients with protein intakes <1.2 g/kg/day, we found a significant negative correlation between age and energy intake ( r =-0.612; P <.001) and between age and protein intake ( r =-0.723; P <.001). Correlations between both energy and protein intakes and age, dialytic age, Kt/V, C-reactive protein, parathyroid hormone, and leptin-BMI were not statistically significant. CONCLUSIONS: This study shows that dietary energy and protein intakes are inadequate in the majority of HD patients and are negatively related to the presence of anorexia and age. These data may be potentially useful in the identification of nutritional strategies as well as in improving food intake in HD patients.

Aged↗
PubMed2005

Branched-chain amino acids: the best compromise to achieve anabolism?

PURPOSE OF REVIEW: The anorexia-cachexia syndrome is highly prevalent in patients suffering from acute and chronic diseases, including cancer, chronic renal failure and liver cirrhosis. Once it has developed, it significantly influences the clinical course of the underlying disease, simultaneously impinging on patients' quality of life. Unfortunately, currently available therapeutic strategies do not appear to greatly impact on patients' morbidity, mortality and quality of life. More effective therapies are needed to promote appetite and food intake, to preserve lean body mass, and to ameliorate patients' psychological distress. RECENT FINDINGS: Branched-chain amino acids are neutral amino acids with interesting and clinically relevant metabolic effects. Their potential role as antianorexia and anticachexia agents was proposed many years ago, but only recent experimental studies and clinical trials have tested their ability to stimulate food intake and counteract muscle wasting in anorectic, weight-losing patients. By interfering with brain serotonergic activity and by inhibiting the overexpression of critical muscular proteolytic pathways, branched-chain amino acids have been shown to induce beneficial metabolic and clinical effects under different pathological conditions. SUMMARY: Based on the available data, branched-chain amino acids appear to exert significant antianorectic and anticachectic effects, and their supplementation may represent a viable intervention not only for patients suffering from chronic diseases, but also for those individuals at risk of sarcopenia due to age, immobility or prolonged bed rest, including trauma, orthopedic or neurologic patients.

Amino Acids, Branched-Chain↗
PubMed2005

Switch from bicarbonate hemodialysis to hemodiafiltration with online regeneration of the ultrafiltrate (HFR): effects on nutritional status, microinflammation, and beta-microglobulin.

BACKGROUND: Hemodiafiltration (HFR) with on-line regeneration of the ultrafiltrate, a technique of hemodiafiltration in which the ultrafiltrate passes through a cartridge containing uncoated charcoal, has been shown to be safe, simple, and well tolerated and has been claimed to improve nutritional status or to prevent its deterioration while decreasing the inflammatory response via a reduced production of proinflammatory cytokines. The purpose of the present prospective study was to ascertain whether HRF improves the nutritional status, reduces microinflammation, and decreases serum beta2-microglobulin levels in patients with end-stage renal disease (ESRD). METHODS: Eight patients, four males and four females, with a mean age of 49.4 +/- 16.8 years, stable on hemodialysis over a period of 8.7 +/- 6.1 years and on standard 4-4.5 h three-times-a-week bicarbonate hemodialysis, were switched to three-times-a-week, 4-h HFR. At baseline and every two months for 12 months at mid-week, serum levels of urea, creatinine, albumin, total cholesterol, C-reactive protein, fibrinogen, complement, ferritin, beta2-microglobulin, intact parathyroid hormone (PTH), hemoglobin concentrations, and hematocrit and the EPO weekly dose were determined. At baseline and at the end of the study, the Malnutrition Inflammatory Score (MIS) was calculated. RESULTS: Nutritional and inflammatory parameters remained constant during the 12-month period of the study. After 12 months of HFR, the MIS trended to be lower, but the difference was not statistically significant. Serum beta2-microglobulin and PTH levels remained constant during all time intervals. Neither hematocrit nor hemoglobin changed over the course of the study as well as the weekly EPO dose. CONCLUSION: The change from bicarbonate hemodialysis to HFR was safe and well tolerated but was not associated with an improvement of nutritional and inflammatory parameters or a reduction of serum beta2-microglobulin levels.

Analysis of Variance↗
PubMed2004

Therapy of muscle wasting in cancer: what is the future?

PURPOSE OF REVIEW: The aim of the present review is to provide insights into the future therapeutic approaches to cancer-related muscle wasting that flow from the progressive knowledge of mechanisms regulating muscle mass in health and disease. RECENT FINDINGS: Cancer cachexia is a severely debilitating and life-threatening paraneoplastic syndrome accounting for approximately 20% of cancer deaths. The prominent clinical feature of cancer cachexia is the progressive loss of muscle mass, which is substantially not reversible with any of the currently available nutritional, metabolic or pharmacological approaches. Cancer cachexia has long been considered a late event in the natural history of cancer patients, thus condemning them to merely palliative interventions. The accumulating evidence that the metabolic and molecular derangements ultimately leading to muscle wasting are operating early after tumour onset, even when weight loss is minimal or absent, is strengthening the view that cancer cachexia should be considered an early phenomenon. SUMMARY: Currently, despite scientific and economic efforts, the therapy of cancer-related muscle wasting has a poor success rate. Present knowledge of the intracellular mechanisms involved in muscle homeoastasis is prompting continuous research aimed at developing more effective and selective therapeutic tools for the prevention and treatment of muscle loss in cancer.

Cachexia↗
PubMed2004

Anorexia and serum leptin levels in hemodialysis patients.

BACKGROUND AND AIMS: Hyperleptinemia is a common feature in hemodialysis (HD) patients. However, the role of increased serum leptin levels in the pathogenesis of HD-related anorexia is still controversial. The purpose of the present prospective study was to ascertain whether hyperleptinemia is causally implicated in the pathogenesis of HD-related anorexia. METHODS: We measured the serum leptin levels and the serum leptin/body mass index (BMI) ratio in 24 healthy subjects and in 49 end-stage renal disease patients on maintenance HD. HD patients were subdivided into anorexic (14/49, 28.5%) and non-anorexic (35/49, 71.5%) according to a questionnaire discriminating for the presence of anorexia-related symptoms. RESULTS: Calorie (kcal/kg/day) and protein (g/ kg/day) intakes were significantly lower in anorexic than in non-anorexic patients (20.1 +/- 1.1 vs. 27.9 +/- 1.3, p = 0.004, and 0.82 +/- 0.05 vs. 1.19 +/- 0.05, p = 0.001, respectively). Accordingly, serum albumin, total lymphocyte count, mid-arm muscle circumference, and the protein equivalence of nitrogen appearance (PNA) were significantly lower in anorexic patients. The serum leptin concentration (ng/ml) was significantly higher in HD patients than in controls, in males (15.33 +/- 3.4 vs. 3.7 +/- 0.3, p = 0.003) and in females (42.3 +/- 7.2 vs. 10.5 +/- 1.3, p = 0.03). Similarly, serum leptin/BMI ratio was significantly higher in HD patients than in controls, in males (0.56 +/- 0.1 vs. 0.16 +/- 0.02, p = 0.0028) and in females (1.8 +/- 0.2 vs. 0.4 +/- 0.04, p < 0.0001). However, serum leptin levels were similar in anorexic and in non-anorexic patients, in males (15.3 +/- 5.6 vs. 16.9 +/- 4.2, p = 0.85) and in females (46.6 +/- 12.9 vs. 47.4 +/- 9.4, p = 0.96). No differences were observed between the 2 groups in the serum leptin/BMI ratio, in males (0.59 +/- 0.2 vs. 0.58 +/- 0.14, p = 0.92) and in females (1.5 +/- 0.4 vs. 1.8 +/- 0.3, p = 0.94). Similarly, no statistically significant differences in terms of serum leptin levels and leptin/BMI ratio were observed between patients with dietary energy intake of <30 or > or =30 kcal/kg/day and between those with a dietary protein intake of <1.2 or > or =1.2 g/kg/day. No significant correlations were found between serum leptin levels and PNA, albumin, cholesterol, total lymphocytes number, weight change, C-reactive protein, fibrinogen, ferritin, and complement. CONCLUSION: The present results indicate that mechanisms other than increases in serum leptin levels might be involved in the pathogenesis of HD-related anorexia.

Aged↗
PubMed2003

Tumor-induced changes in host metabolism: a possible role for free tryptophan as a marker of neoplastic disease.

Tumor growth is associated with a number of metabolic abnormalities. Glucose metabolism is deranged as frequently revealed by an impaired oral glucose tolerance test. Lipoprotein lipase activity is depressed, resulting in hypertrigliceridemia after an exogenous lipid load. Also protein metabolism is deranged in cancer patients, as revealed by changes of plasma amino acid profile. Our previous studies on plasma amino acids have shown that increased plasma free tryptophan levels are a frequent finding in cancer patients. To sustain a possible role for free tryptophan as a marker of neoplastic disease, we measured its plasma concentrations in 241 patients with cancer. Plasma free tryptophan concentrations were found to be significantly elevated with respect to healthy controls in patients with breast, lung, colon, stomach, and cancer from various origin. The sensitivity of this marker in predicting the presence of the tumor was highest for stomach and lung cancer patients. High plasma free tryptophan concentrations seem to be directly related to the presence of the tumor, since in breast cancer patients they returned to within normal range after eradicative surgery.

Amino Acids↗
PubMed2003

Increased muscle proteasome activity correlates with disease severity in gastric cancer patients.

OBJECTIVE: To investigate the state of activation of the ATP-ubiquitin-dependent proteolytic system in the skeletal muscle of gastric cancer patients. SUMMARY BACKGROUND DATA: Muscle wasting in experimental cancer cachexia is frequently associated with hyperactivation of the ATP-dependent ubiquitin-proteasome proteolytic system. Increased muscle ubiquitin mRNA levels have been previously shown in gastric cancer patients, suggesting that this proteolytic system might be modulated also in human cancer. METHODS: Biopsies of the rectus abdominis muscle were obtained intraoperatively from 23 gastric cancer patients and 14 subjects undergoing surgery for benign abdominal diseases, and muscle ubiquitin mRNA expression and proteasome proteolytic activities were assessed. RESULTS: Muscle ubiquitin mRNA was hyperexpressed in gastric cancer patients compared to controls. In parallel, three proteasome proteolytic activities (CTL, chymotrypsin-like; TL, trypsin-like; PGP, peptidyl-glutamyl-peptidase) significantly increased in gastric cancer patients with respect to controls. Advanced tumor stage, poor nutritional status, and age more than 50 years were associated with significantly higher CTL activity but had no influence on TL and PGP activity. CONCLUSIONS: These results confirm the involvement of the ubiquitin-proteasome proteolytic system in the pathogenesis of muscle protein hypercatabolism in cancer cachexia. The observation that perturbations of this pathway in gastric cancer patients occur even before clinical evidence of body wasting supports the thinking that specific pharmacologic and metabolic approaches aimed at counteracting the upregulation of this pathway should be undertaken as early as cancer is diagnosed.

Biopsy↗
PubMed2003

Duodenal pathology and clinical-immunological implications in common variable immunodeficiency patients.

OBJECTIVES: Common variable immunodeficiency (CVID) is an immunological disorder characterized by defective antibody production. An increased prevalence of celiac disease has been suggested in patients with this disorder. This study aimed to assess duodenal pathology and its clinical implications in these patients. METHODS: A total of 32 consecutive CVID patients with anemia or GI symptoms were enrolled. Patients underwent upper endoscopy, and biopsy specimens were taken in the descending duodenum for histological assessment. A blood sample was obtained to determine immunoglobulin and Hb levels and to evaluate the CD4+ T-lymphocyte count. Body mass index was calculated for all patients. RESULTS: Histological assessment of duodenal specimens revealed the presence of villous atrophy in 10 (31.2%) patients, a feature of nodular lymphoid hyperplasia in five (15.6%), and mild duodenitis in two (6.3%), whereas normal histology was observed in the remaining 15 (46.9%) patients. Patients with villous atrophy had anemia more frequently than those without, whereas the frequency of persistent diarrhea did not differ between these two groups. Moreover, both CD4 levels and body mass index were significantly lower in patients with atrophy than in controls. CONCLUSIONS: Duodenal villous atrophy is very frequent in symptomatic CVID patients, with relevant clinical and immunological implications. Specifically, this histological alteration is significantly associated with anemia, malnutrition, and low blood CD4+ lymphocyte levels.

Common Variable Immunodeficiency↗
PubMed2002

Nutritional and metabolic support in patients undergoing bone marrow transplantation.

Bone marrow transplantation (BMT) is a sophisticated procedure consisting of the administration of high-dose chemoradiotherapy followed by intravenous infusion of hemopoietic stem cells to reestablish marrow function when bone marrow is damaged or defective. BMT is used in the treatment of solid tumors, hematologic diseases, and autoimmune disorders. Artificial nutrition, total parenteral nutrition in particular, is provided to patients undergoing BMT to minimize the nutritional consequences of both the conditioning regimens (eg, mucositis of the gastrointestinal tract) and complications resulting from the procedure (eg, graft versus host disease and venoocclusive disease of the liver). Although artificial nutrition is now recognized as the standard of care for BMT patients, defined guidelines for the use of artificial nutrition in this clinical setting are lacking. During the past 2 decades, artificial nutrition in BMT patients has moved from simple supportive care to adjunctive therapy because of the possible benefits, not strictly nutritional, of specialized nutritional intervention. Although data exist documenting the beneficial role of special nutrients, such as lipids and glutamine, in the management of BMT recipients, the results obtained to date are controversial. The reasons for this controversy may reside in the heterogeneity of the patients studied and of the study designs. This review focuses on the need to correctly identify the different patterns of BMT to achieve reproducible and reliable data, which may in turn be used to devise precise guidelines for the use of specialized artificial nutrition in BMT patients.

Adult↗
PubMedDate not supplied

Effects of simvastatin administration in an experimental model of cancer cachexia.

OBJECTIVE: We evaluated whether statins, in view of their anti-inflammatory properties, may effectively prevent the onset or modulate the severity of muscle wasting during cancer cachexia. METHODS: Simvastatin was administered to rats bearing the Yoshida AH-130 ascites hepatoma, a well-studied cytokine-dependent experimental model of cancer cachexia. RESULTS: Quite surprisingly, the drug negatively affected the wasting pattern induced by the AH-130 hepatoma. In fact, the administration of simvastatin to tumor hosts induced a further weight reduction of all the tissues examined except for the soleus, in the absence of significant effects of simvastatin on tumor growth or on food intake. No effects were observed after simvastatin administration in control animals, with the exception of a significant (P < 0.05) reduction in heart weight. CONCLUSIONS: Simvastatin administration, although capable of negatively modulating the inflammatory response, did not prevent muscle wasting in this experimental model of cancer cachexia. Moreover, the further muscle loss observed in simvastatin-treated tumor-bearing animals suggests that a note of caution should be introduced in treating cancer patients with statins in view of the possible occurrence of harmful side effects.

Animals↗