K.P. Pandya

Generation of hydroxyl radicals during benzene toxicity

In the present study, an attempt has been made to detect formation of formaldehyde and degradation of deoxyribose as indicators of hydroxyl radical generation during benzene toxicity

Subcutaneous kerosene toxicity in albino rats

Biochemical, histopathological, and hematological parameters were studied in male Wistar rats after repeated subcutaneous administration of commercial kerosene (0.5 ml/kg body wt, 6 days a week) for a period of 35 days. At necropsy, treatment-related increases in the weights of liver, spleen, and peripheral lymph nodes were noted. Correspondingly, there was an increase in DNA, RNA, protein, and lipid contents of liver and spleen. Histopathological examination of liver, spleen, thymus, kidney, adrenal, and lymph nodes revealed treatment-related lesions. Similarly, biochemical indices studied in liver revealed an increase in alkaline phosphatase and a decrease in benzo[a]pyrene hydroxylase levels. Furthermore serum cholinesterase, carboxylesterase, and albumin levels were significantly diminished while serum alkaline phosphatase levels were found to be greatly enhanced. The findings might be related as the likely systemic effects in workers upon percutaneous kerosene exposure during work.

Modulation of benzene toxicity by an interferon inducer (6MFA)

Repeated intraperitoneal administration of benzene (1.0 ml/kg body wt) for 3 days produced leucopenia, lymphocytopenia and an increased number of nucleated cells in the bone marrow and significantly decreased organ weights of thymus (P less than 0.001) and spleen (P less than 0.001) in female albino rats. Iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly increased as a result of benzene exposure. Prior administration of 6MFA, an interferon inducer with immunomodulating potential, was found to ameliorate some of the adverse effects of benzene as well as restoration of hepatic architecture histologically. Lipid peroxidation and iron content were both normalised, whereas superoxide dismutase activity was further increased and the number of lymphocytes and bone marrow cells returned to normal. Pretreatment of animals with 6MFA was able to enhance the SRBC antibody titre in benzene-treated immunosuppressed animals. The beneficial effects of 6MFA in the amelioration of the acute toxicity of benzene therefore assume certain significance.

Interaction of endosulfan and metepa in rats

Repeated administration of endosulfan or metepa or their mixture did not induce any significant histological changes in the organs examined in male rats. Similarly, the activity of different enzymes assayed here showed no significant alterations. The level of endosulfan did not differ significantly in presence or absence of metepa in the samples of blood, brain, fatty tissue, kidney, liver and testis. The observations do not suggest any kind of additive or antagonistic effects or potentiation of each compound in presence of the other, at the doses and duration studied in male rats.

Accumulation of low molecular weight (bleomycin detectable) iron in bone marrow cells of rats after benzene exposure

An accumulation of low molecular weight (LMW) bleomycin detectable iron in the bone marrow was observed after administration of benzene (IP 0.5 ml/kg, daily) for 5 and 10 days in female albino rats. However, this LMW iron was not detectable in the bone marrow of rats from the control group. Studies of bone marrow fractionation showed that the maximum accumulation of this LMW iron was in the mitochondrial fraction. An increase in the activity of superoxide dismutase and lipid peroxidation was also noticed in the benzene exposed groups.

Involvement of iron and free radicals in benzene toxicity

The 59Fe distribution after a single i.v. injection of 59Fe citrate in rats exposed to benzene was studied in circulating erythrocytes and organs up to period of 1 hr to 14 days. The iron content was significantly higher in bone marrow and liver compared to a control group of animals. A few cells with hemosiderin granules were observed in the benzene-administered group. Benzene increased lipid peroxidation in the liver and bone marrow and iron accelerated it further. Superoxide dismutase activities measured in terms of epinephrine auto-oxidation, an indirect measure of superoxide anion generation was enhanced in the benzene-treated groups. The data suggest the involvement of oxygen activation in benzene toxicity.

Hepatic metabolism of heme in rats after exposure to benzene, gasoline and kerosene

Abstractδ-Aminolevulinic acid (ALA) synthetase, δ-ALA dehydratase and heme oxygenase activities were studied in the liver of albino rats, 3 and 20 h after i.p. administration of benzene, gasoline, and kerosene. δ-ALA synthetase activity was increased markedly after benzene administration, while gasoline and kerosene treated groups showed decreased enzyme activity. Inhibition of δ-ALA dehydratase activity was observed in all three groups, but heme oxygenase activity was unchanged.

Modulation of benzene induced toxicity by protein A

Administration of benzene (i.p. 1.0 mL/kg body weight) for 3 consecutive days produced leucopenia and lymphocytopenia in female albino rats. In addition, the total iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly (P < 0.001) increased. Low molecular weight (LMW) bleomycin-detectable iron accumulated only in bone marrow. Prior administration of Protein A (PA), a multipotent immunostimulant and interferon inducer (60 micrograms/kg body weight, i.v. twice weekly for 2 weeks), ameliorated most of the adverse effects of benzene. PA restored the changes in hepatic histological architecture, reversed leucopenia and superoxide dismutase activity, lipid peroxidation, total iron content and LMW iron content of bone marrow were normalized. Isozymes of glutathione-S-transferase (alpha, pi, mu) which decreased following benzene exposure increased in PA pretreated benzene exposed rats. This study suggests that pretreatment with PA modulates the toxicity of benzene.

Release of 2-thiobarbituric acid reactive products from glutamate or deoxyribonucleic acid by 1,2,4-benzenetriol or hydroquinone in the presence of copper ions

Cytotoxic effects of various quinone compounds are thought to be due to the formation of semiquinone free radicals. Hydroquinone and 1,2,4-benzenetriol in the presence of copper ions release from glutamate or DNA aldehydic products capable of reacting with 2-thiobarbituric acid (TBA). The formation of TBA reactive products (TBAR) was greater in the presence of 1,2,4-benzenetriol in comparison with hydroquinone. Complete inhibition of formation of TBAR from glutamate by 1,2,4-benzenetriol and copper was observed in the presence of catalase, thiourea and mannitol. Albumin and superoxide dismutase offered substantial protection. Complete protection of formation of TBAR from DNA was observed in the presence of catalase and thiourea. Presence of albumin, mannitol and superoxide dismutase caused only partial inhibition. The formation of TBAR from glutamate or DNA is dependent on copper ion concentration. The present data indicate that hydroquinone and 1,2,4-benzenetriol in the presence of copper ions can lead to the formation of reactive hydroxyl radicals which can release TBAR from glutamate or DNA.

Biochemical changes induced by naphthalene after oral administration in albino rats

Biochemical alterations were observed in albino rats after oral administration of naphthalene for 10 days. The changes were significant in the liver where increases in liver weight, lipid peroxidation and aniline hydroxylase activity were observed. A slight increase of alkaline phosphatase activity was observed in the liver and eye. No significant change was observed in the kidney.