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B S Kaphalia

Publications and source records attributed to B S Kaphalia.

At least 19 recordsLinked to original sources
PubMed1995

Hematopoietic toxicity of linoleic acid anilide: importance of aniline.

The purpose of this study was to investigate the role of hydrolysis products of linoleic acid anilide (LAA), i.e., aniline and linoleic acid (LA), in the toxicity to the hemopoietic system, especially to the spleen. To achieve this, the parent compound (LAA) and its putative hydrolysis products, i.e., aniline or linoleic acid (LA), were given to male SD rats at equimolar doses (0.7 mmol/kg) in 0.25 ml mineral oil by gavage, daily, for 14 days. The controls received equal volumes of vehicle only. Five animals from each group were euthanized at Days 1, 7, and 28 following the last dose. At all time points, spleen weights increased in the LAA- and aniline-treated rats, but spleen to body weight ratios were increased only at Days 1 and 7 in these groups. No changes were observed in the LA-treated rats at any time point. RBC counts were decreased in the LAA and aniline groups at Days 1 and 7, whereas hemoglobin content was decreased by 20 and 13% in the LAA- and aniline-treated rats, respectively, only at Day 1. Methemoglobin content in the LAA and aniline groups also increased by 76 and 101%, respectively, at Day 1. Serum transaminases (AST and ALT) decreased in the LAA, aniline, and LA groups but the decreases were more consistent in the LA group. Serum IgA increased in the LAA and aniline groups only at Day 1. Splenic iron content was increased 381, 486, and 51% in the LAA-treated rats and 474, 491, and 58% in the aniline-treated rats at Days 1, 7, and 28, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗
PubMed1992

Methylene dianiline: acute toxicity and effects on biliary function.

4,4'-Methylene dianiline (4,4'-diaminodiphenylmethane, DAPM), which is used in the polymer industry, causes hepatobiliary damage in exposed humans. Our objectives were to characterize the acute toxicity of DAPM in liver, particularly on secretion of biliary constituents and on biliary epithelial cell gamma-glutamyl transpeptidase (GGT) activity. Biliary cannulas were positioned in Sprague-Dawley male rats under pentobarbital anesthesia. After 1 hr of control bile collection, each rat was given 250 mg DAPM/kg (50 mg/ml) po in 35% ethanol or 35% ethanol only; bile was collected for a further 4 hr. Groups of rats were also examined for liver injury and biliary function at 8 and 24 hr after DAPM. Four hours after DAPM administration, main bile duct cells were severely damaged with minimal damage to peripheral bile ductule cells. Focal periportal hepatocellular necrosis and extensive cytolysis of cortical thymocytes occurred by 24 hr. Serum indicators of liver injury were elevated by 4 hr and continued to rise through 24 hr. By 4 hr, biliary protein concentration was increased 4-fold while concentrations of biliary bile salt, bilirubin, and glutathione were decreased by approximately 80, 50, and 200%, respectively. DAPM also induced a striking effect on biliary glucose with an approximately 20-fold increase. Histochemical staining of main bile duct GGT was absent by 8 hr after DAPM. Bile flow was diminished by 40% at 4 hr; three of five rats had no bile flow by 8 hr and none had any bile flow by 24 hr. These results indicate that DAPM rapidly diminishes bile flow and alters the secretion of biliary constituents and is highly injurious to biliary epithelial cells.

Administration, Oral↗
PubMed1992

Covalent binding of ethylene dibromide and its metabolites to albumin.

The present study was undertaken to determine covalent binding of [1,2-14C]ethylene dibromide (EDB) to albumin under in vivo and in vitro conditions. For the in vivo covalent binding, 25 mg/kg body weight of [1,2-14C]EDB was given daily to male rats for 12 consecutive days and the animals were sacrificed at 24 h following the last dose. Blood was withdrawn from inferior vena cava in heparinized tubes and plasma was separated, dialyzed against ice-cold 10 mM phosphate buffer (pH 7.4) and then subjected to size-exclusion high-performance liquid chromatography (SE-HPLC). A major radioactive peak eluted at an elution volume corresponding to 65,000 dalton molecular mass was found to be associated to albumin at a level of 0.14 nmol equivalent EDB/mg protein. For the in vitro covalent binding, human plasma or purified albumin was incubated with [1,2-14C]EDB in the presence of phenobarbital-treated rat liver microsomes and NADPH-generating system for 2 h at 37 degrees C. The 100,000 x g supernatant of the incubation mixture was dialyzed extensively and analyzed as described for the in vivo studies. Approximately 0.28 nmol equivalent EDB/mg protein was found to be associated to albumin (about 2-fold higher than the in vivo binding). Binding of 14C-label to albumin under in vivo and in vitro conditions was further supported by the affinity chromatography of albumin fraction isolated by SE-HPLC. Reversed-phase HPLC analysis of pronase digest of the albumin obtained from in vitro studies indicated formation of several amino acid adducts of EDB and/or its metabolites. Structure elucidation of such amino acid adducts will be helpful in developing a relatively non-invasive method of measuring the EDB exposure.

Administration, Oral↗
PubMed1992

Toxic response of linoleic acid anilide in female rats.

The toxicity of linoleic acid anilide (LAA) and heated linoleic acid anilide (HLAA) was studied in female rats. Female Sprague-Dawley rats were given 250 mg/kg of LAA or HLAA in mineral oil, by gavage, on alternate days for two weeks. Control rats received an equal volume of mineral oil. The animals were sacrificed at day 1, 7 and 28 following the last dose. Organ-to-body weight ratio was increased for spleen in both LAA and HLAA treated rats at day 1. Lung, kidney and brain showed increases in this ratio at some time point, whereas, thymus in the HLAA group showed a decrease at day 28. Among blood parameters, red blood cells and hemoglobin content decreased in both LAA and HLAA treated groups at day 1 and in the LAA group at day 7. Serum IgA levels increased throughout the study in both treatment groups and were more pronounced in HLAA treated rats. Splenic T-helper lymphocyte numbers decreased in the HLAA group at day 1, whereas, other cell types were not affected. The changes observed in female rats are comparable to our previous findings in male rats and relatively minor in relation to sex differences. These results further support that hemopoietic system is an early target of fatty acid anilide toxicity.

Anilides↗
PubMed1992

Toxic response to repeated oral administration of 2-chloroethyl linoleate in rats.

In the present study, we investigated the toxic response to repeated oral administration of 2-chloroethyl linoleate (2-CEL) in male rats at 250 mg/kg body weight for 2 weeks on alternate days (total 7 doses). Control rats received an equal volume of mineral oil. The five animals from each group were sacrificed on days 1, 7 and 28 following the last dose. No significant changes were observed in body weight, as well as organ-to-body weight ratios due to 2-CEL treatment. The red blood cell counts increased significantly in 2-CEL treated animals at day 28 as compared to the controls. Elevated counts of platelets, monocytes and eosinophils and low counts of basophils and large unstained cells were also observed at some time points in 2-CEL treated rats. Significantly reduced activities of total serum lactate dehydrogenase (LDH), aspartate aminotransferase and alanine aminotransferase were found at most of the time points except for LDH at day 28. Adenosine triphosphatase activity was also significantly reduced in liver mitochondrial fraction at all time points. Histopathological studies showed consistent centrilobular lesions (incidence 4/4) in the liver consisting of hepatocyte vacuolar degeneration and focal necrosis at day 28. A few centrilobular lesions were also observed (incidence 2/4) at day 7, while no changes were observed at day 1. These results indicate that 2-CEL is a hepatotoxin, however, the observed decrease in serum enzyme levels in relation to hepatotoxicity of 2-CEL, needs to be elucidated.

Animals↗
PubMed1991

Toxicity of oleic acid anilide in rats.

In the present investigation, we have studied the toxic potential of oleic acid anilide (OAA) and heated oleic acid anilide (HOAA) in relation to the toxic oil syndrome (TOS). Male Sprague-Dawley rats were given 250 mg/kg of OAA or HOAA in mineral oil by gavage, on alternate days for 2 weeks (total 7 doses). The control rats received an equal volume of mineral oil only. The animals were sacrificed at days 1, 7, and 28 following the last dose. Ratio of organ-to-body weight showed increases in spleen and kidney of HOAA and OAA treated rats, respectively, at day 1 while this ratio for liver in HOAA treated group showed a decrease at day 1. Among blood parameters, white blood cells increased in HOAA treated group at day 1 and in both OAA and HOAA groups at day 28. Mean corpuscular hemoglobin (MCH) and mean cell volume (MCV) also showed increases in the HOAA treated rats at days 7 and 28. Serum lactate dehydrogenase (LDH) decreased in both OAA and HOAA treated rats at day 1, while at day 7 the decrease was confined only to the HOAA group. Serum glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities also decreased at most of the time points. Liver mitochondrial ATPase activity decreased in the HOAA group at day 7 and in the OAA group at day 28. Among serum immunoglobulins, IgA levels increased throughout the study but the changes were more pronounced in HOAA treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilides↗
PubMed1991

Heated linoleic acid anilide: toxicity and relevance to toxic oil syndrome.

The present study was undertaken to investigate toxic potentials of linoleic acid anilide (LAA) and heated linoleic acid anilide (HLAA) and their possible role in the etiology of toxic oil syndrome (TOS). Male Sprague-Dawley rats were given 250 mg/kg of LAA or HLAA in mineral oil through gavage, on alternate days for 2 weeks (total 7 doses). Control rats received an equal volume of vehicle only. The animals were sacrificed at day 1, 7 and 28 following the last dose. Ratio of organ weight/body weight showed a significant increase in lung in LAA group at day 7 while spleen showed remarkable increases in both treatment groups at day 1 and 7. On the other hand, this ratio showed decreases in case of liver, brain and heart at some time points. Among blood parameters, red cell counts and hemoglobin content decreased at day 1 in both LAA and HLAA treated groups, while platelet counts showed an increase. Serum LDH, GOT and GPT activities significantly decreased at day 1 and 7 in both LAA and HLAA treated groups, however, these changes were more prominent in the HLAA treated group. Interestingly, at day 28, these serum enzyme levels recovered to control levels. Both LAA and HLAA treated groups showed a decrease in serum IgM levels at day 1, however, at day 7 only the LAA group showed a significant decrease. IgA levels significantly increased in both groups at all the time points studied and were more pronounced in the HLAA treated group. Similarly, IgG levels also showed increases in both the groups. In addition to serum immunoglobulin changes, alterations in the lymphocyte subpopulations were also observed. While T-cell population decreased, B-cell population remained unchanged. Among T-cell subsets, T-helper cells did not show any change while T-suppressor cells decreased significantly at day 1 in the LAA group and at day 1 and 7 in the HLAA group, but regained control levels at day 28. The biochemical and immunological alterations observed in this study as a result of LAA and HLAA exposure and more so by HLAA further support that the fatty acid anilides may play a role in the etiology of TOS.

Anilides↗
PubMed1991

Synergistic vascular toxicity and fatty acid anilides in the toxic oil syndrome.

The underlying etiology of the toxic oil syndrome may be related to any of several toxic contaminants. The hypothesis is made that two or more toxic compounds may act synergistically to cause vascular damage in the toxic oil syndrome. To support this hypothesis, previous studies are reviewed concerning the remarkable synergistic toxic action of allylamine and beta-aminopropionitrile on the media of blood vessels. Although these toxins are not directly related to the toxic oil syndrome, this previous experimental work emphasizes the possibility that unexplored synergistic actions may be important. Furthermore, the hypothesis that contaminating fatty acid anilides in toxic oil undergo alterations during cooking is supported by high pressure liquid chromatographic analysis. The theoretic metabolism of fatty acid anilides is discussed. Recent data concerning the toxic actions of the anilides of oleic and linoleic acid are given. These data suggest that these anilides induce immunologic alterations that may be similar to those seen in the toxic oil syndrome. In addition, the heated anilides appear to have increased toxicity, supporting the concept that the use of toxic oil in cooking may increase its toxicity.

Allylamine↗
PubMed1991

Heated linoleic acid anilide reduces serum enzyme activities in rats.

In view of possible involvement of fatty acid anilides in toxic oil syndrome (TOS), the effects of linoleic acid anilide (LAA) and heated linoleic acid anilide (HLAA) on the activities of serum enzymes following their oral administration was studied in rats as a function of time. Serum glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities decreased significantly in both LAA and HLAA treated rats at day 4. The decreases, however, were confined to only HLAA treated group at later stages with GOT activity showing significant decrease at day 8 and total lactate dehydrogenase (LDH) as well as GOT and GPT activities at day 12. Liver GOT activity at day 4 and LDH activity at day 8 decreased significantly in both LAA and HLAA treated rats. These findings indicate HLAA components may interact with plasma membranes and thereby, reducing the secretion of the enzymes into the serum.

Alanine Transaminase↗
PubMed1989

Hepatic fatty acid conjugation of 2-chloroethanol and 2-bromoethanol in rats.

To study the formation of fatty acid conjugates of 2-chloroethanol (2-CE) and 2-bromoethanol (2-BE), rats were administered (by gavage) 50 mg/kg of 2-CE and 2-BE in mineral oil and sacrificed on fifth day of the treatment. Hepatic microsomal lipids were extracted, and the fatty acid esters were separated by preparative thin-layer chromotography. The ester fraction was further purified by reverse-phase, high-performance liquid chromatography and analyzed by ammonia chemical ionization mass spectrometry. Pseudomolecular ions (M + NH4+, base peak) at m/z 336/338, 362/364, and 364/366 in a ratio of 3:1 and 380/382 and 408/410 in a ratio of 1:1 confirmed the in vivo formation of 2-chloroethyl palmitate, 2-chloroethyl oleate, 2-chloroethyl stearate, 2-bromoethyl palmitate, and 2-bromoethyl stearate, respectively. These results demonstrate the formation of fatty acid conjugates of 2-CE and 2-BE in vivo. These fatty acid conjugates may be retained in the body for a longer time and cause toxic manifestations.

Animals↗
PubMed1987

Selective pancreatic toxicity of palmitoylpentachlorophenol.

Palmitoylpentachlorophenol (PPCP), which is a lipid conjugate of a xenobiotic compound, has been found in human fat. To study the toxicity associated with PPCP, rats were given 100 mg/kg PPCP and sacrificed at 4, 8 and 12 days. The target organ identified was the exocrine pancreas; no other major organs examined showed any gross or histopathological abnormality. At 4 and 8 days after treatment, focal, spotty vacuolation, and loss of pancreatic acini was observed. Acute inflammatory infiltrate was also observed in parenchyma at all time points and the loss of acinar tissue was resolved through fibrous tissue formation by 12 days. The present study indicates that PPCP has a specific target organ toxicity.

Animals↗
PubMed1985

Organochlorine pesticide residues in mother's milk: a source of toxic chemicals in suckling infants.

A total of 24 samples of mother's milk collected during the first week of lactation from four major cities in India (Karnal, Bangalore, Calcutta and Bombay) were analysed for the estimation of organochlorine pesticides (OCPs). alpha-HCH, p,p'-DDE, and p,p'-DDT were generally the main contaminants. The average total 1,1,1-trichloro-2,2-bis (p-chlorophenyl) ethane (DDT) levels stand at 0.05, 0.11, 0.19 and 0.22 p.p.m. (whole-milk basis) in the samples from Bangalore, Calcutta, Karnal and Bombay respectively. In the same order total hexachlorocyclohexane (HCH) levels were around 0.01, 0.03, 0.03 and 0.05 p.p.m. Wide variations among OCP levels observed in the present study have no relation with the fat content of the various samples. The samples from Calcutta and Bombay showed significantly high levels of OCPs. The daily intake of total HCH and DDT residues calculated for the suckling infant was significantly higher in the present study when compared with the WHO recommended value.

Fats↗
PubMed1981

DDT and BHC residues in some body tissues of goats, buffalo, and chickens, Lucknow, India.

Muscle, liver, brain, and abdominal body fat samples of goats, buffalo, and chickens, all common meat sources in India, were analyzed by gas-liquid chromatography (GLC) for residues of DDT and benzene hexachloride (BHC). A few samples of goat and buffalo bone marrow were also included. Relatively high residue levels were found in body fat and bone marrow compared with other tissues. DDT and BHC residue levels were highest in chicken body fat, averaging 4.157 ppm sigma DDT and 3.879 ppm BHC. DDT content was much higher in goat and buffalo bone marrow than in the corresponding body fat. DDT levels in brain samples were highest (0.138 ppm) in buffalo. p,p'-TDE levels were higher than p,p'-DDE levels in buffalo; overall DDT levels were lowest in goats. BHC residues were generally low in buffalo; alpha-BHC accounted for most BHC residues in brain tissues. Greater accumulations of DDT and BHC were found in leg muscles than in breast muscles of chickens.

Animals↗