Biomedical subjects

H M Chan

Publications and source records attributed to H M Chan.

At least 55 records · Page 3Linked to original sources

PubMed1998

Autotransplantation of parathyroid glands into subcutaneous forearm tissue for renal hyperparathyroidism.

BACKGROUND: Autotransplantation of diseased parathyroid glands into subcutaneous adipose tissue has been mentioned previously, but as far as we know there is no previous systemic study concerning parathyroid function after subcutaneous autotransplantation. METHODS: From January 1993 to June 1996, total parathyroidectomy and autotransplantation were carried out in 46 patients with renal hyperparathyroidism. The symptoms and signs before operation were intractable pruritus in 29 patients (63%), bone pain in 27 patients (58.7%), general weakness in 17 patients (37%), soft tissue calcification in 15 patients (32.6%), bone fracture in one patient, and failure to thrive in one patient. Twenty-four patients (group A) underwent autotransplantation of 60 mg of a diffuse hyperplastic parathyroid gland into subcutaneous forearm tissue, and 22 patients (group B) underwent autotransplantation of 15 pieces (60 mg) of 1 mm3 tissue into forearm muscles, as mentioned previously. Four patients in group A and one in group B who had high levels of intact parathyroid hormone (I-PTH) immediately after operation were excluded. After the operation, calcium carbonate, 1.5 to 16 gm daily, and calcitriol, 0.25 to 1.5 micrograms/daily, were prescribed according to the patients' calcium levels. RESULTS: After 6 months, all patients in both groups were given calcium carbonate, 1 gm/day, and calcitriol, 0.25 microgram/day, for parathyroid suppression, and none had to take more medicine to maintain calcium levels. There were no significant differences between the two groups regarding serum calcium, phosphorous, alkaline phosphatase, and I-PTH levels 1 week, 3 to 6 months, and 1 year after operation. Eighteen patients in group A and 19 patients in group B had normal levels of I-PTH 1 year after operation. In the follow-up period from 1 to 3 1/2 years, only one patient in group A had a subnormal I-PTH level and one in group B had graft-dependent hyperparathyroidism. CONCLUSIONS: We therefore suggest that autotransplantation of a parathyroid gland into forearm subcutaneous tissue for renal hyperparathyroidism is as effective as autotransplantation into forearm muscles and can be done easier.

Adolescent↗

PubMed1997

Toxaphene congeners differ from toxaphene mixtures in their dysmorphogenic effects on cultured rat embryos.

The presence of persistent organic pollutants, including the pesticide toxaphene has been reported even in remote regions such as the Arctic and is becoming a health concern. The technical mixture of toxaphene contains over 800 different congeners. The numbers of prevalent congeners, however, decrease along the food chain. About 20 major congeners are found in fish, eight in marine mammals and only two major ones in human, 2-exo,3-endo,5-exo,6-endo,8,8,10,10-octachlorobornane (T2) and 2-exo,3-endo,5-exo,6-endo,8,8,9,10,10-nonachlorobornane (T12). Embryotoxicity of these individual congeners is not known, as previous studies focused on the toxaphene technical mixture. We studied the relative dysmorphogenic activity of toxaphene technical mixture and individual congeners (T2 and T12) using rat embryo culture. Explanted embryos (0-2 somites) were treated for 48 h with concentrations of 0 (DMSO 0.01%), 100, 1000 and 5000 ng/ml of either (a) toxaphene technical mixture; (b) T2; (c) T12; or (d) a 50:50 mixture of T2 and T12. The treatment period corresponds to gestational days (GD) 10-12, a period within the critical time of morphogenesis and organogenesis. Both the technical mixture and the two individual congeners had a significant adverse effects on the total morphological score, somite number, head and crown rump length and the central nervous system scores of embryos. All treatments caused a high incidence of central nervous system defects. The T2 and T12 congeners differed in their spectrum of abnormalities as exposure to T2 caused limb and flexion defects which were not observed with the T12 congener. Differences were also observed in the type of toxicity and the target sites between the technical mixture and the congeners. T2 showed a more potent adverse effect on the morphological score as compared to the technical mixture. Both T2 and T12 were less inhibitory on growth than the technical mixture as indicated by crown-rump length but they showed a stronger inhibitory effect on otic system development. The mixture of T2 + T12 showed a synergistic effect on decreasing crown-rump and head length. Conversely, the combination of T2 and T12 inhibited the strong adverse effect of the individual congeners on otic development. The results suggest environmentally predominant toxaphene congeners can have organ specific embryotoxic effects not predicted by the toxaphene technical mixture.

Animals↗

PubMed1997

2'-Substitution of cocaine selectively enhances dopamine and norepinephrine transporter binding.

Few studies have characterized the effect of substituents at the 2'-position of cocaine on transporter binding potency and selectivity. We synthesized 2'-OH-, 2'-F- and 2'-acetoxy-cocaines and compared their binding potencies for rat dopamine, norepinephrine and 5-hydroxytryptamine transporters to cocaine, 3'-OH-, 4'-OH-, 2'-OH,4'-I-cocaine derivatives, and to the transporter selective ligands WIN 35,428, nisoxetine and paroxetine. Unlike most substitutions, 2'-OH- and 2'-acetoxy-groups increased cocaine's binding potency for the dopamine transporter (10- and 4-fold, respectively). These substituents also enhanced binding to the norepinephrine transporter (52- and 35-fold, respectively) but had less effect on 5-hydroxytryptamine transporter binding. 2'-Hydroxylation also enhanced binding of 4'-I cocaine, an analog with low DA binding potency. The ability of 2'-substituents to substantially increase cocaine binding potency and to alter selectivity for brain transporters indicates the potential importance of the 2'-position in transporter binding.

Animals↗

PubMed1997

Acute fulminant neuropathy in a patient with Churg-Strauss syndrome.

We report a patient with an acute neuropathy initially mimicking Guillain-Barré syndrome, both clinically and electrophysiologically. Persistent eosinophilia, positive antineutrophil cytoplasmic antibody and eosinophilic vasculitis in sural nerve biopsy later confirmed Churg-Strauss syndrome. Since vasculitic neuropathy can present in an acute and fulminant form, the role of early antibody testing and sural nerve biopsy in atypical cases of acute neuropathy is emphasized.

Antibodies, Antineutrophil Cytoplasmic↗

PubMed1997

Evaluation of the population distribution of dietary contaminant exposure in an Arctic population using Monte Carlo statistics.

Organochlorines and heavy metals have bioaccumulated in Arctic wildlife, which is an important food source for the Inuit. In this study, we have developed a statistical model to describe the population distribution of contaminant exposure and the usual intake of the high-end contaminant consumers. Monte Carlo methods are used to account for variations due to seasonal dietary pattern and contaminant concentrations. Distribution of the dietary intake of the contaminants of most concern-mercury, polychlorinated biphenyls (PCBs), chlordane, and toxaphenes-are described. Over 50% of the residents had dietary exposure levels exceeding the tolerable daily intake or provisional tolerable daily intake for Hg, toxaphene, and chlordane (83, 91, and 71% for men and 73, 85, and 56% for women, respectively). The high-end consumers (i.e. the 95th centile) have intake levels 6 times higher than the provisional tolerable weekly intake of Hg, and over 20 times the tolerable daily intake of chlordane and toxaphene. Assessment of health risks of the relative high contaminant exposure in this community must also consider the nutritional, economical, cultural, and social importance of these traditional foods. A comprehensive risk management scheme has yet to be developed.

Adult↗

PubMed1997

The protective effect of metallothionein against lipid peroxidation caused by retinoic acid in human breast cancer cells.

The treatment of breast cancer by retinoic acid (RA) may be mediated by lipid peroxidation. Expression of metallothionein (MT) in cancer cells, however, can protect against lipid peroxidation by scavenging hydroxyl radicals. In this study, a two-by-six factorial design was used to investigate the interactive effects of all-trans-RA and zinc (Zn)-induced MT on the growth of two human breast cancer cell lines differing in basal expression of MT and estrogen receptors; MCF7 cells express estrogen receptor, BT-20 cells do not. Cells were treated with Zn to induce MT and then treated with six RA concentrations. Cell proliferation, lipid peroxidation, MT protein, MT mRNA and glutathione concentrations were measured. BT-20 cells expressed higher constitutive MT concentrations than MCF7 cells. MT was significantly increased by Zn treatment in BT-20 cells but not in MCF7 cells. Low RA concentrations stimulated growth proliferation but higher concentrations inhibited cell proliferation. Elevated RA concentrations increased lipid peroxidation as measured by thiobarbituric acid reactive substances. There was a significant negative correlation between lipid peroxidation and cell proliferation. Growth inhibition and lipid peroxidation were reduced by Zn pretreatment in BT-20 cells but not in MCF7 cells. RA increased MT levels in both cell lines, which suggests that RA may generate free radicals which will induce MT mRNA expression. Glutathione did not appear to be a significant factor. Therefore, induction of MT by Zn may modulate the growth inhibitory effects of RA in human breast cancer cells. One mechanism of growth inhibition may be through increased lipid peroxidation. Induction of MT by RA may be one explanation for acquired RA resistance in cancer.

Breast Neoplasms↗

PubMed1996

Architectural design and tools to support the transparent access to hospital information systems, radiology information systems, and picture archiving and communication systems.

The fragmentation of the electronic patient record among hospital information systems (HIS), radiology information systems (RIS), and picture archiving and communication systems (PACS) makes the viewing of the complete medical patient record inconvenient. The purpose of this report is to describe the system architecture, development tools, and implementation issues related to providing transparent access to HIS, RIS, and PACS information. A client-mediator-server architecture was implemented to facilitate the gathering and visualization of electronic medical records from these independent heterogeneous information systems. The architecture features intelligent data access agents, run-time determination of data access strategies, and an active patient cache. The development and management of the agents were facilitated by data integration CASE (computer-assisted software engineering) tools. HIS, RIS, and PACS data access and translation agents were successfully developed. All pathology, radiology, medical, laboratory, admissions, and radiology reports for a patient are available for review from a single integrated workstation interface. A data caching system provides fast access to active patient data. New network architectures are evolving that support the integration of heterogeneous software subsystems. Commercial tools are available to assist in the integration procedure.

Computer Systems↗

PubMed1995

Arctic indigenous women consume greater than acceptable levels of organochlorines.

Exposure to polychlorinated biphenyls and organochlorine pesticides through traditional food resources was examined for Arctic Indigenous women living in two cultural and environmental areas of the Canadian Arctic--one community representing Baffin Island Inuit in eastern Arctic and two communities representing Sahtú Dene/Métis in western Arctic. Polychlorinated biphenyls, toxaphene, chlorobenzenes, hexachlorocyclohexanes, dichlorodiphenyltrichloroethane, chlordane-related compounds and dieldrin were determined in local food resources as normally prepared and eaten. Quantified dietary recalls taken seasonally reflected normal consumption patterns of these food resources by women in three age groups: 20-40 y, 41-60 y and > or = 61 y. There was wide variation of intake of all organochlorine contaminants in both areas and among age groups for the Sahtú. Fifty percent of the intake recalls collected from the Baffin Inuit exceeded the acceptable daily intake for chlordane-related compounds and toxaphene, and a substantial percentage of the intake records for dieldrin and polychlorinated biphenyls exceeded the acceptable or tolerable daily intake levels. Primary contributing foods to organochlorine contaminants intake for the Baffin Inuit were meat and blubber of ringed seal, blubber of walrus and mattak and blubber of narwal. Important foods contributing organochlorine contaminant to the Sahtú Dene/Métis were caribou, whitefish, inconnu, trout and duck. The superior nutritional benefits and potential health risks of traditional food items are reviewed, as are implications for monitoring organochlorine contaminant contents of food, clinical symptoms and food use.

Adult↗

PubMed1995

Comparison of serum CA15-3 and CEA in breast cancer.

The monoclonal antibodies CA15-3 were developed against the two antigens 115D8 of the human milk fat globule membrane and DF3 of breast cancer. CA15-3 was assayed radioimmunologically and CEA was analysed using the enzyme immunoassay. Normal control was achieved in 32 healthy women, the mean values for CA15-3 were 11.5 +/- 3.0 u/ml, range from 7.9 to 16.9 u/ml. We compared serum levels of CA15-3 and CEA in 121 patients with histologically proved breast carcinoma. CA15-3 levels above 25 u/ml and CEA levels above 5 ng/ml were considered positive values. 31 of 121 patients studied had elevated CA15-3 levels (sensitivity: 25.6%) and 21 of 121 patients had positive CEA levels (sensitivity 17.4%). 92 of the breast cancer patients (76%) did not have metastatic disease. In this group CA15-3 sensitivity was 7.6%, while CEA sensitivity was 6.5%. Mean values were 15.1 +/- 6.6 u/ml for CA15-3 and 1.78 +/- 2.47 ng/ml for CEA. 29 patients (24%) had metastatic disease. In this group, CA15-3 sensitivity was 82.8% and CEA sensitivity was 51.7% (P < 0.05). Mean values for CA15-3 were 147.5 +/- 175.9 u/ml and 16.9 +/- 24.0 ng/ml of CEA. With regard to the correlation of two tumor markers with clinical course patients had significantly higher levels of CA15-3 than of CEA in metastatic breast cancer. This result suggests CA15-3 to be the more sensitive and more specific of the two for metastatic breast cancer detection and monitoring.

Adult↗

PubMed1994

Copper-metallothionein from the toxic milk mutant mouse enhances lipid peroxidation initiated by an organic hydroperoxide.

The toxic milk mutation is an autosomal recessive mutation found in an inbred C57BL/6J strain of mice which results in an excessive hepatic accumulation of copper (Cu), mostly associated with metallothionein (MT). The possible toxicological significance of elevated levels of hepatic copper-metallothionein (Cu-MT) was assessed. The effects of Cu-MT on lipid peroxidation (LP) initiated by an organic peroxide were investigated in an in vitro rat liver microsomal incubation system. Addition of Cu-MT (3 microM) could significantly enhance (100%) LP induced by addition of tertiary-butyl hydroperoxide (t-BHP, 0.1 mM). Similar incubations of Cu-MT in the absence of t-BHP showed negligible LP. Addition of copper sulfate at high concentrations (100 microM) also increased t-BHP induced LP, but the enhancement was less pronounced than observed with Cu-MT addition. Chelation of copper with bovine serum albumin and triethylene-tetramine tetrahydrochloride eliminated the enhancement of LP by Cu-MT. Evidence is provided on degradation of MT and release of free Cu in the incubation system. Additions of deferoxamine were also found to prevent LP. Therefore, chelatable Cu, released from Cu-MT, may be responsible for the enhancement of the iron-dependent LP in this system but Cu-MT alone in the absence of iron cannot initiate LP. These in vitro results suggest that conditions resulting in high cellular levels of Cu-MT may exhibit a predisposition to oxidative stress.

Analysis of Variance↗

PubMed1994

Abdominal wall hernia complicating continuous ambulatory peritoneal dialysis.

Continuous ambulatory peritoneal dialysis (CAPD) is a well-established treatment modality for end-stage renal disease. Abdominal wall hernia is not uncommon in patients on CAPD. Two factors are responsible for the occurrence of these hernias: anatomically weak sites and increased intraperitoneal pressure by the dialysate. Abdominal wall hernia was reviewed in 44 patients on CAPD from 1987 through 1991. Eight abdominal hernias (5 inguinal, 2 incisional and 1 umbilical) were found during CAPD treatment (18.18%). Surgical treatment was applied in 6 symptomatic hernias (5 inguinal and 1 incisional). After surgery, 5 patients returned to CAPD without recurrence and the remaining one died of strangulated incisional hernia. Our series shows that: (1) a detailed examination of the preexisting hernia and repair prior to CAPD treatment are suggested. (2) symptomatic abdominal wall hernia should be evaluated carefully and treated promptly. (3) awareness of the complication of these hernias can reduce the morbidity and mortality.

Adult↗

PubMed1993

Nephrotoxicity of repeated injections of cadmium-metallothionein in rats.

Cadmium-metallothionein (Cd-MT) may have a role in the pathogenesis and irreversibility of Cd nephrotoxicity. In the present study, rats were injected with 0.3 mg Cd/kg body wt per week as Cd-MT for 5 consecutive weeks and a group of rats (n = 3) was killed 24 hr after each injection. A group of three rats was kept for an additional week after the 5 weeks of Cd-MT injection for recovery. After the first injection, urinary Cd and protein levels and kidney/body wt ratio were increased. The electrophoretic pattern of urinary protein showed increased excretion of low-molecular-weight proteins, especially after the first injection of Cd-MT. Tubular cell necrosis occurred after the first week with renal Cd levels of only 10 micrograms/g and gradually progressed to severe necrosis with inflammation in 3 weeks and then to interstitial fibrosis in 5 weeks. The levels of Cd and MT in kidney increased with repeated injection of Cd-MT, but renal Cd was about 40 micrograms/g after 5 weeks of injection. Urinary Cd and MT levels progressively increased during the Cd exposure period, but returned to pretreatment levels during the sixth week (recovery period). Renal cell necrosis and inflammation were absent at the sixth week, but interstitial fibrosis persisted. This study indicates that nephrotoxicity of Cd in this model is related to urinary excretion of Cd-MT and that renal cell injury may be independent of Cd in the renal cortex. Nephrotoxicity occurs at levels much lower than the proposed critical concentration for Cd (200 micrograms Cd/g) following long-term exposure to CdCl2. However, in the absence of continued Cd exposure from liver or circulation, the Cd-MT-induced renal damage is reversible.

Analysis of Variance↗

PubMed1993

Mobilization of hepatic cadmium in pregnant rats.

Mobilization of hepatic cadmium (Cd) in pregnant rats was investigated. Female Sprague-Dawley rats (200-250 g) were injected subcutaneously, daily with 1.0 mg Cd/kg body weight as CdCl2 for 8 days. A group of these rats was made pregnant. Copper (Cu), zinc (Zn), Cd, and metallothionein (MT) concentrations in the liver, kidney, and plasma of the control and Cd-injected, pregnant and nonpregnant rats, were compared. The hepatic Cd concentration of the Cd-injected rats decreased by 40% during pregnancy and became significantly lower than that of the nonpregnant Cd-injected rats. On the other hand, there was a concomitant increase (60%) of Cd concentrations in the kidney of the Cd-injected pregnant rats. MT in the Cd-injected rats also showed a similar pattern of decrease in hepatic concentrations and increase in renal concentrations during pregnancy. Both Cd and MT contents in the placenta of the Cd-injected rats were higher than those of the control and there was a significant increase over the gestational period. Plasma Cd and MT concentrations of the Cd-injected pregnant rats were higher than those of Cd-injected nonpregnant rats. These results suggest that pregnancy can mobilize the hepatic Cd which can be transferred to the kidney and placenta through the blood plasma. Moreover, the blood urea nitrogen levels of the pregnant Cd-injected rats were increased on Gestation Day 21 and 7 days after delivery, indicating signs of Cd nephropathy. The hepatic Cd, Cu, Zn, and MT concentrations of the newborn rats, however, were unaltered by Cd injections. Therefore, it is possible that pregnancy may induce a high risk of Cd nephrotoxicity in women with chronic Cd exposure.

Animals↗

PubMed1993

Nephrotoxicity in rats following liver transplantation from cadmium-exposed rats.

Although kidney is considered as the critical organ for cadmium (Cd) toxicity, little is known about the transport of Cd to kidney after chronic exposure. In order to study this transfer, male Lewis rats (150-200 g) were given eight injections (sc) of CdCl2 (3 mg Cd/kg) over 2 weeks which resulted in increases of tissue Cd and metallothionein (MT) concentrations (223 and 1850 micrograms/g, respectively, in the liver and 118 and 873 micrograms/g, respectively, in the kidney). Livers from Cd-injected rats were transplanted to age-matched control healthy Lewis rats and the recipient rats were killed at 2 to 47 days after transplantation. The levels of Cd and MT in the liver of recipient rats were decreased (106 and 1503 micrograms/g, respectively) with time after surgery. On the other hand, renal Cd and MT levels were markedly increased (195 and 1468 micrograms/g, respectively) and most of the Cd in the kidney was bound to MT. About 100 ng/ml of Cd and MT were detected in the plasma of recipient rats by ELISA. There was some periportal fibrosis in the liver due to transplant procedure which did not anastomose hepatic arteries. There was an increase in blood urea nitrogen levels in rats transplanted with Cd-containing liver. In addition, both necrosis and inflammation were observed in the epithelial cells in the proximal tubules in the kidney which typically occurs in chronic Cd toxicity. These results suggest that the major source of renal Cd in chronic Cd exposure may be derived from hepatic Cd which is transported in the form of Cd-MT in blood plasma.

Animals↗

PubMed1993

Pregnancy-associated changes in plasma metallothionein concentration and renal cadmium accumulation in rats.

Pregnancy-associated changes in metallothionein (MT) concentrations in blood plasma were examined using a competitive enzyme-linked immunosorbent assay with a rabbit polyclonal antibody to rat liver MT. Plasma MT of pregnant rats significantly increased after 8 days of gestation and remained high during pregnancy and for 7 days after delivery. Gel filtration showed that both Cu and Zn were associated with the plasma MT of pregnant rats. These results suggest that plasma MT may play a role in the transport of essential metals such as Cu and Zn to fetus during pregnancy, but the source of plasma MT is unknown. Injections of cadmium chloride and cadmium-metallothionein to pregnant rats further increased the plasma MT concentrations. After injection of CdCl2, both MT and Cd concentrations in the liver of the pregnant rats were significantly lower than those of the nonpregnant rats, whereas renal Cd and MT levels were higher in pregnant rats. This increased accumulation of Cd in the kidney of pregnant rats may be related to the increase of plasma MT during pregnancy. About 5% of 6 pg of in vitro added Cd (20 pg/ml) was bound to the MT in the plasma. Therefore, Cd may be transported by the circulating MT to the kidney, leading to an increase in renal accumulation of Cd in pregnant rats.

Animals↗

PubMed1993

Enterolith ileus as a complication of duodenal diverticulosis--one case report and review of the literature.

Duodenal diverticulosis is not a rare condition. Usually of little clinical significance, it can produce a variety of disorders such as malabsorption, hemorrhage, diverticulitis, and obstruction. The rarest complication appears to be enterolith formation and obstruction. The case presented is a 70-year-old woman with the chief complaints of intermittent abdominal pain and vomiting. At laparotomy, duodenal diverticulitis and one enterolith obstructing the distal ileum were found. The literature review presents the other 26 cases with small bowel obstruction due to an enterolith formed within a small bowel diverticulum. The diagnosis can be established only by documenting the normalcy of the gallbladder and the presence of duodenal or jejunal diverticula.

Aged↗

PubMed1992

Exogenous metallothionein and renal toxicity of cadmium and mercury in rats.

The relative tissue distribution and toxicity of cadmium (Cd) and mercury (Hg) in the liver and kidneys of rats when the metals are administered as either inorganic salts or complexed with MT were studied. Male Sprague-Dawley rats were injected (i.v.) with Cd or Hg inorganic salt of chloride or in a complex of MT at a dose of 0.3 mg/kg body weight. The concentration of MT and metals in plasma and urine was monitored for 7 days, at the end of which the rats were killed. Injection of both HgCl2 and Hg-MT induced the synthesis of MT only in the kidney but not in the liver, whereas CdCl2 and Cd-MT injections induced MT synthesis in both liver and kidney, respectively. Plasma MT levels increased 3 days after CdCl2 but not after HgCl2 injection, suggesting that hepatic MT may be an important source of plasma MT under our experimental conditions. Renal toxicity was observed morphologically and by an increase in blood urea nitrogen, plasma creatinine, proteinuria in rats injected with Cd-MT and both forms of Hg. Urinary MT excretion was significantly elevated in Cd-MT injected rats compared with those injected with CdCl2. However, HgCl2 and Hg-MT injected rats showed no significant difference in urinary MT excretion. The magnitude in the renal accumulation of Hg is similar after the administration of Hg-MT or HgCl2, but our findings suggest that the site of epithelial injury may be different. Injury effects of Hg-MT localized mainly in the terminal portions of the proximal convoluted tubule and the initial portions of the proximal straight tubule whereas inorganic Hg caused necrosis in pars recta segments of the proximal tubule.

Animals↗

PubMed1992

The relative importance of glutathione and metallothionein on protection of hepatotoxicity of menadione in rats.

The effects of induction of metallothionein (MT) on the toxicity of menadione were investigated in rat liver slices. The protective role of hepatic glutathione (GSH) was also studied and compared to that of MT. A 3-h incubation of rat liver slices with menadione (100-300 microM) containing medium (37 degrees C, pH 7.4, 95%O2:5%CO2) resulted in cellular toxicity, as shown by changes in cytosolic K, Ca and GSH concentrations and lactate dehydrogenase (LDH) leakage. A dose-dependent decrease in cytosolic K and GSH was observed concomitant with an increase in cytosolic Ca and LDH leakage after incubation with menadione. Pretreatment of rats with zinc sulphate (ZnSO4) (30 mg/kg body wt.) increased MT levels in liver slices and suppressed the toxicity of menadione. Intracellular GSH concentrations in liver slices were either depleted or increased by injection of rats with buthionine sulfoximine (BSO), (4 mmol/kg body wt.) and N-acetyl-L-cysteine (NAC) (1.6 g/kg body wt.), respectively. Intracellular GSH was found to be crucial in protection against menadione toxicity. Menadione toxicity was increased when the rats were injected with sodium phenobarbital (PB) (4 x 80 mg/kg body wt.). Pretreatment with Zn provided partial protection against menadione toxicity in liver slices from both BSO- and PB-injected rats. These findings suggest that induction of MT synthesis does protect against quinone-induced toxicity, but the role may be secondary to that of GSH. The mechanisms by which MT protect against menadione toxicity are still unclear but may involve protection of both redox cycling and sulphydryl arylation.

Acetylcysteine↗