Ameliorative effect of resveratrol against cymoxanil-mancozeb induced toxicity in rats.

This study was conducted to evaluate the cymoxanil-mancozeb (CM) toxicity and investigate the ameliorative effect of resveratrol (Res) against cymoxanil-mancozeb toxicity. Forty rats were divided into four groups; the first group was used as a control group, the second group was exposed to Res only at a dose of 20 mg/kg body weight for 4 weeks, and the third group was administered CM only at a dose of 799 mg/kg body weight for 4 weeks, The fourth group was co-treated with Res+CM for 4 weeks. Blood samples were analyzed for hematological and biochemical parameters. The comet assay was done on liver and blood specimens and histopathological examinations of the liver and intestine. The results demonstrated that CM exposure caused a significant increase in WBCs, lymphocytes, granulocytes, monocytes ALT, AST, ALP, and GGT, and total cholesterol and triglycerides levels accompanied by a decrease in HGB, HCT, RBCs and MCV, MCH, MCHC, HDL and glucose levels with no significant DNA damage in liver and blood. CM mixture induced severe pathological changes in small intestine and liver. Co-treatment of Res with CM improved hematological picture, lipid and glucose profiles also liver enzymes and decreased changes in the architecture of the liver and intestine.

Protective effect of avenanthramides against cisplatin induced nephrotoxicity in rats.

OBJECTIVE: The aim of this study is to inspect the ameliorative effect of avenanthramides (AVA) on CP nephrotoxicity in Sprague-Dawley rats. MATERIALS AND METHODS: Blood samples were collected for the determination of hematological parameters. Creatinine, blood urea nitrogen (BUN), and tumor necrosis factor-α (TNF-α) were measured in serum. Specimens from both kidneys were taken for histopathological examinations. RESULTS: Administration of AVA resulted in significant decrease in the level of creatinine and TNF-α when compared with CP group. Histopathologically, CP-induced vacuolar degeneration and necrosis of the kidney tubules. Administration of AVA ameliorates the histopathological alterations induced by CP. CONCLUSION: AVA can be considered as a protective agent for kidneys during administration of CP. The protective effect of AVA may be related to the reduction of TNF-α which implicated in the pathogenesis of CP nephrotoxicity.

Mancozeb fungicide-induced genotoxic effects, metabolic alterations, and histological changes in the colon and liver of Sprague Dawley rats.

The present study was designed to evaluate genotoxic markers of mancozeb exposure and withdrawal in colon and liver tissues together with histological changes in the gastrointestinal tract of Sprague Dawley rats. Thirty rats were divided into three equal groups; group I: treatment, 250 mg/kg mancozeb dissolved in corn oil administered twice weekly for 7 weeks; group II: withdrawal, the same treatment as group I after which animals were untreated for 5 weeks; group III: control, administered corn oil on the same schedule as group I for 7 weeks. All administrations were by oral gavage. Serum samples were analyzed for biochemical parameters. The comet assay and histopathological examinations were done on liver and colon specimens. The results demonstrated that mancozeb exposure caused significant increases in triglycerides and total cholesterol accompanied by decreases in glucose levels, with extensive DNA damage in liver and colon together with pathological changes in stomach, colon, and liver. Mancozeb withdrawal for 5 weeks improved the lipid and glucose profiles and decreased the degree of DNA damage and changes in the architecture of the stomach, colon, and liver. We concluded that discontinuing exposure to mancozeb fungicide for 5 weeks could ameliorate the adverse effects induced by 7 weeks of exposure to mancozeb. A longer withdrawal time may further reduce the observed genotoxicity.

Co-administration of glutathione alleviates the toxic effects of 2,3,7,8 TCDF on the DNA integrity of sperm and in the testes of mice.

This study aimed to investigate the toxic impact prompted in the testes of adult mice exposed to 2,3,7,8-tetrachlorodibenzofuran (TCDF). Four groups of 12 mice each were used in the present study. Group 1 mice were kept as control and administered corn oil only. Group 2 animals were given glutathione (GSH) in a dose of 100 mg/kg body weight by oral gavage twice a week. Group 3 was given TCDF orally twice per week, in a dose of 0.5 µg/kg body weight for 8 weeks. Group 4 was administered GSH orally in a dosage of 100 mg/kg body weight plus TCDF twice a week for 8 weeks. Animals were sacrificed after 2, 4, and 8 weeks of exposure, serum samples were collected for estimation of testosterone hormone, the testes were dissected and one part was used for estimation of superoxide dismutase (SOD), malondialdehyde (MDA), lactate dehydrogenase (LDH), and 3ß-hydroxysteroid dehydrogenase. Another portion of the testis was kept in formalin for histopathological examination. The results showed that the activities of SOD were decreased while the levels of lipid peroxidation MDA were increased in the testicular tissues of the exposed mice. The serum testosterone level and the steroidogenic enzyme 3ß-hydroxysteroid dehydrogenase activity of testicular homogenate were essentially decreased in TCDF-treated mice. A significant increment in the testicular LDH activity in testicular tissues was recorded in mice exposed to TCDF. The percentage of DNA chromatin disintegration was significantly increased in TCDF-treated mice. Histopathological changes were recorded in TCDF-exposed group as degenerative changes of the seminiferous tubules with formation of spermatid giant cells at 2 weeks in addition to exhaustion of germinal epithelium and detachment of the germ cells from the basal lamina at 4 and 8 weeks. Co-administration of GSH could reestablish MDA and LDH levels besides reduction in percentage of sperm DNA damage and improvement of the testicular tissue architecture.

Ameliorative effects of thymoquinone on titanium dioxide nanoparticles induced acute toxicity in rats.

Although the nanoparticles had a beneficial activity, it had also adverse effects as a result of generation of oxidative stress. The current study aimed to assess the ameliorative effect of thymoquinone (TQ) on titanium dioxide nanoparticles (TiO2 NPs) induced acute toxicity in male rats. Forty-eight male rats were distributed into four equal groups (12 rats each). Group (1) received single oral dose of TiO2 NPs (300 mg/kg), Group (2) received TiO2 NPs and TQ (20 mg/kg), Group (3) received TQ and group (4) received only the vehicle and served as control group. TiO2 NPs intoxicated group showed increased the level of lipid peroxidation product (LPO), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and decreased the level of antioxidants and testosterone. Vascular and degenerative changes in the liver and testes were observed by light microscopy as well as presence of TiO2 NPs in the lysosomes by electron microscopy. Treatment with TQ revealed improvement of the biochemical parameters, histology and ultrastructure of the liver and testes. It was concluded that acute intoxication of rats with TiO2 NPs induced adverse effect in the liver and testes. Administration of TQ has an ameliorative effect against oxidative stress induced by TiO2 NPs intoxication.

Protective effects of thymoquinone and avenanthramides on titanium dioxide nanoparticles induced toxicity in Sprague-Dawley rats.

The protective effect of thymoquinone (TQ), the major active ingredient of Nigella sativa seeds, and avenanthramides (AVA) enriched extract of oats on titanium dioxide naonparticles (TiO2 NPs) induced toxicity and oxidative stress in Sprague-Dawley (SD) rats was investigated. Sixty rats were divided into 6 equal groups. The first, second, third, fourth and fifth groups received TiO2 NPs, TiO2 NPs and TQ, TiO2 NPs and AVA, TQ only, or AVA only for 6 weeks. The sixth group served as the control. Exposure to TiO2 NPs resulted in increased liver enzyme markers, oxidative stress indices, tumor necrosis factor alpha (TNF-α) and DNA damage. Histopathological alterations were also observed in the liver, brain, lung, kidney, heart and testes. Co-administration of TQ and AVA with TiO2 NPs decreased the level of liver enzymes, oxidative stress, TNF-α and DNA damage. Furthermore, TQ and AVA increased the total antioxidant and glutathione (GSH) levels. In conclusion, TiO2 NPs induce hazardous effects in different organs and are closely related to oxidative stress. TQ and AVA have antioxidative and anti-inflammatory effect against the detrimental effect of TiO2 NPs.