K. Pratap Reddy

Protective role of Centella asiatica on lead-induced oxidative stress and suppressed reproductive health in male rats

Centella asiatica has been mentioned in ancient ayurvedic text of the Indian system of medicine for its properties to promote intelligence. The objective of the present study was to investigate the beneficial effects of C. asiatica on lead-induced oxidative stress and suppressed reproductive performance in male rats. Significant decrease in the weights of testes and epididymis were observed in lead treated animals. Exposure to lead acetate significantly increased malondialdehyde levels with a significant decrease in the superoxide dismutase and catalase activities in the liver, brain, kidneys and testes of rats. Epididymal sperm count, viable sperms, motile sperms and HOS-tail coiled sperms decreased significantly in lead-exposed rats. Testicular steroidogenic enzyme activities also decreased significantly in lead-exposed rats. No significant changes in the selected reproductive variables were observed in the plant extract alone treated rats. Whereas, co-administration of aqueous extracts of C. asiatica to lead exposed rats showed a significant increase in the weights of reproductive organs, reduction in lead-induced oxidative stress in the tissues and improvement in selected reproductive parameters over lead-exposed rats indicating the beneficial role of C. asiatica to counteract lead-induced oxidative stress and to restore the suppressed reproduction in male rats.

Protective effects of resveratrol against cisplatin-induced testicular and epididymal toxicity in rats.

This study investigated the probable protective effect of resveratrol against cisplatin-induced testicular and epididymal toxicity in rats. Body weights of the animals showed no significant changes after cisplatin administration. Conversely, the weights of testis, and accessory sex organs reduced significantly. The daily sperm production and epididymal sperm quantity and quality were decreased in cisplatin treated rats. The circulatory levels of testosterone and activity levels of testicular 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase were significantly decreased after cisplatin treatment. The activity levels of superoxide dismutase and catalase were decreased with an increase in the levels of lipid peroxidation and H2O2 generation in the testis and epididymis of cisplatin treated rats, suggesting the cisplatin-induced oxidative stress. The biochemical findings were supplemented by histological examination of testis. Reduced tubular size, decreased spermatogenesis and deterioration in architecture were observed after cisplatin treatment. Administration of resveratrol alone has no significant effect on testicular and epididymal metabolism. On the other hand, administration of resveratrol ameliorated cisplatin-induced alterations in testicular and epididymal oxidative damage, suppressed steroiodgenesis and spermatogenesis and restored testicular architecture. In conclusion, resveratrol possesses multimechanistic protective activity that can be attributed to its steroidogenic and antioxidant actions.

Role of melatonin in mitigating chemotherapy-induced testicular dysfunction in Wistar rats

Abstract Testicular cancer is the most common cancer affecting men of reproductive age, and its incidence is increasing steadily. A regimen of cisplatin (P), vinblastin (V) and bleomycin (B) (PVB) is the standard chemotherapy for testicular cancer. Though PVB-based chemotherapy has been widely used against germ cell tumors, it is associated with induction of oxidative toxicity and a transient or permanent loss of fertility. However, the mechanism of action of PVB on the testis is not thoroughly elucidated. Using a rat model, we investigated the persistence of the effects of PVB on steroidogenesis, spermatogenesis and testicular oxidative status and architecture. Further, we have also studied whether administration of melatonin has any protective effect on testicular physiology in the PVB-treated rats, since melatonin exerts influence on the antioxidant defense system. The body weight of the PVB-treated rats did not show significant change as compared with the control group. Significant decrease in the weight of the testis was observed with a reduction in volume in the PVB-treated rats. Administration of PVB caused a reduction in the testicular steroidogenesis and spermatogenesis. The circulatory levels of testosterone were also significantly reduced with an elevation of FSH and LH in the PVB-treated rats. Testicular architecture was severely affected with a reduction in seminiferous tubule diameter and epithelial height. The activities of superoxide dismutase and catalase were decreased while the levels of lipid peroxidation increased significantly in the testis of the PVB-treated rats indicating depletion of antioxidant defence system and elevation of oxidative stress. Co-administration of melatonin mitigated these changes in the PVB-treated rats.

Melatonin reduces oxidative stress and restores mitochondrial function in the liver of rats exposed to chemotherapeutics

This study was undertaken to investigate whether administration of melatonin protects PVB-Induced oxidative and metabolic toxicity in the liver of Wistar rats. Adult male Wistar rats were intraperitoneally injected with either melatonin or PVB (cisplatin, vinblastine, and bleomycin) alone or combination for a period of 9 weeks. A significant increase in lipid peroxidation levels and decrease in catalase and superoxide dismutase activity levels were observed in the liver mitochondria of rats treated with PVB indicating increased oxidative stress. PVB treatment significantly decreased the succinate dehydrogenase activity with a significant increase in lactate dehydrogenase, glucose-6-phosphate dehydrogenase, aspartate aminotransaminase, alanine aminotransaminase, and glutamate dehydrogenase activities indicating deranged hepatic metabolism. Melatonin administration, on the other hand was found to significantly improve PVB-Induced biochemical changes, bringing them closer to the controls. The results from the study provide evidence that treatment with PVB affects hepatic metabolism in rats by inducing oxidative stress followed by decreasing mitochondrial oxidation and also point towards the clinical potential of melatonin as an adjuvant therapy to conventional chemotherapeutic regimens.

Reproductive and paternal mediated developmental toxicity of benzo(a)pyrene in adult male Wistar rats

In this study, we evaluated reproductive toxic effects of benzo(a)pyrene (BaP) in adult male Wistar rats. Rats received intra-peritoneal injections containing BaP at a dose of 1, 10 or 100 μg per kg bw on alternate days for 60 days and were analyzed for fertility. Control and experimental male rats were cohabited with control female rats and sperm positive female rats were analyzed for paternal-mediated reproductive and developmental toxicity. Dose dependent reduction in the litter size and crown rump length was apparent in pups sired by experimental males. The developmental landmarks were comparable among pups in all groups except for the delay in testis descent and vaginal opening which was observed in experimental pups. After completion of fertility studies, rats were sacrificed and analyzed for reproductive endpoints. The relative weights of the testes, caput epididymis, cauda epididymis, seminal vesicles and prostate gland were decreased significantly in BaP exposed animals. Daily sperm production and epididymal sperm count, motility and viability decreased significantly in a dose dependent manner in BaP treated rats. Also, there was a dose dependent decrease in the testicular steroidogenic enzyme activities. Additionally, serum testosterone levels were decreased in BaP treated animals. In silico studies revealed the binding affinity of BaP to simulated StAR protein in the hydrophobic tunnel region. It can be concluded that chronic exposure to sub-lethal doses of BaP affects steroidogenesis and spermatogenesis resulting in reduced fertility in adult male rats.

The protective effects of zinc in lead-induced testicular and epididymal toxicity in Wistar rats

The aim of this study was to investigate the beneficial effects of zinc (Zn) in preventing lead (Pb)-induced reproductive toxicity in Wistar rats. The rats were divided into four groups, namely, control group, Pb group, Zn group, and Pb + Zn group. Animals were exposed to Pb (819 mg of Pb/L) or Zn (71 mg of Zn/L) or both through drinking water for 65 days. Rats exposed to Pb showed decreased weights of testes and accessory sex organs. Significant decrease in the testicular daily sperm production, epididymal sperm count, motility, viability, and number of hypoosmotic tail coiled sperm was observed in Pb-exposed rats. Testicular 3β- and 17β-hydroxysteroid dehydrogenase activity levels and circulatory testosterone levels were also decreased significantly in Pb-exposed rats. A significant increase in the lipid peroxidation products with a significant decrease in the activities of catalase and superoxide dismutase were observed in the testes and epididymis of Pb-exposed rats. Moreover, the testicular architecture showed lumens devoid of sperm in Pb-exposed rats. Supplementation of Zn mitigated Pb-induced oxidative stress and restored the spermatogenesis and steroidogenesis in Pb-exposed rats. In conclusion, cotreatment of Zn is effective for recovering suppressed spermatogenesis, steroidogenesis, elevated oxidative status, and histological damage in the testis of rats treated with Pb.

Behavioral and neurochemical consequences of perinatal exposure to lead in adult male Wistar rats: protective effect by Centella asiatica

The present study evaluated the protective effects of Centella asiatica (CA) leaf extract on behavioral deficits and neurotoxicity in adult rat exposed to lead during perinatal period. Adult Wistar rats were exposed to 0.15% lead acetate (Pb) from gestation day 6 through drinking water and the pups were exposed lactationally to Pb till weaning. Significant perturbations in locomotor activity and exploratory behavior were observed in rats exposed to Pb during perinatal period. The levels of lipid peroxidation increased significantly with a reduction in levels of glutathione and activity levels of acetylcholinesterase and antioxidant enzymes in hippocampus, cerebrum, cerebellum, and medulla of brains excised from Pb-exposed rats. Oral supplementation of CA during postweaning period provided significant protection against Pb-induced behavioral impairments and neurotoxicity, without chelating tissue Pb levels. The possible neuroprotective efficacy of CA may be due to its antioxidant potential but not by lowering effects of brain Pb content.

Effects of maternal exposure to aflatoxin B1 during pregnancy on fertility output of dams and developmental, behavioral and reproductive consequences in female offspring using a rat model.

Abstract A suboptimal in utero environment can have detrimental effects on the pregnancy and long-term adverse “programing” effects on the offspring. Aflatoxin B1 is one of the potent reproductive toxicants and currently detected in both milk and tissues. This article focuses on the effects of prenatal exposure to graded doses of aflatoxin B1 on the pregnancy outcomes of dams and postnatal developments of the female offspring, since these issues have ethological relevance in both animals and humans. Pregnant Wistar rats were injected intramuscularly with vehicle or aflatoxin B1 (10, 20, 50 or 100 μg/kg body weight/day) on days 12–19 of gestation. At parturition, newborns were observed for clinical signs of toxicity and survival. The female offspring were examined through a battery of tests in order to evaluate their developmental, behavioral and reproductive end points. All animals were born alive. The litter size of the aflatoxin B1 treated rats was comparable to the controls. However, the birth weight of the pups in the experimental group was significantly lower when compared to controls. Significant and persistent lags in cliff avoidance, negative geotaxis, surface rightening activity and ascending wire mesh, with a delay in elapsed time for vaginal opening were detected in the female progeny exposed to aflatoxin B1 during embryonic development. The locomotor activity and exploratory behavior in experimental females were significantly decreased than that of controls. Embryonic exposure to aflatoxin B1 also resulted in prolonged stress response, irregular estrus and suppressed fertility output in the progeny at their adulthood. These results indicate that in utero exposure to aflatoxin B1 severely compromised postnatal development of neonatal rats and caused irregular estrus that was accompanied by suppressed fertility output.

Protective effects of Abelmoschus moschatus seed extract on neurotransmitter system of developing brain of Wistar rats with gestational and post-natal exposure of sodium fluoride

Aims: Fluoride known environmental pollutant and also neurotoxicant and functions through oxidative stress and excitotoxicity mechanisms in brain. Balanced levels of neurotransmitters (NTs) are essential for healthy condition while their imbalanced status leads to illnesses and associated abnormalities. The present study focused on maternal as well as post-natal exposure of fluoride and its effects on NTs and protective effects of Abelmoschus moschatus seed extract through regulation of NTs system. Materials and Methods: The pregnant Wistar rats were randomly categorized into six groups of five animals each. Group I is of control rats which received normal tap water. Group II is sodium fluoride (NaF) exposed group with 20 ppm (or 20 mg/kg body wt.) in their drinking water. Group III and Group IV rats were treated with A. moschatus aqueous (AMAE) and ethanolic (AMEE) extract (at the rate of 300 mg/kg body wt./day/rat), respectively, along with NaF water (20 ppm). Group V and Group VI rats were treated with AMAE and AMEE (300 mg/kg body wt./day/rat) respectively. On 1st, 7th, 14th, 21st, and 30th day (postpartum days), the pups were sacrificed to assess NTs levels of brain of all experimental groups.Results: The epinephrine and glutamate levels were increased, while nor-epinephrine, dopamine, serotonin, and acetylcholine levels were decreased significantly (P < 0.001) in NaF-fed rats with respect to control group and were restored on the treatment of AMAE and AMEE toward control. In addition, monoamine oxidase (MAO-A and MAO-B) activity also increased in NaF intoxicated rats than the control, and its activity was reverted to normal in NaF-received rats along with AMAE and AMEE. Discussion: These findings suggested that NaF exposure during developmental stages alter the NTs levels where as their levels are regulated on the treatment of A. moschatus toward NaF. AMEE showed better efficacy over AMAE. Conclusion: It can be concluded that the seed extract of Abelmoschus has therapeutically significant efficacy in protection from NaF toxicity.

Induction of oxidative stress by benzo(a)pyrene in the epididymis of Wistar rats

The present study was undertaken to evaluate the effect of sub-chronic exposure to benzo(a)pyrene on the antioxidant system and histology of rat epididymal sperm. Intraperitoneal administration of benzo(a)pyrene to male Wistar rats at doses between 1 and 100 µg/kg body weight for 60 days entailed a decrease in the weight of the epididymis (caput and cauda), seminal vesicle, and prostate, while the body weight was not affected. Epididymal sperm reserves were reduced in a dose-dependent manner. Indicators of lipid peroxidation were increased while activities of superoxide dismutase and catalase in all three epididymal regions decreased. Histological malformations were observed in the epididymis. Exposure to benzo(a)pyrene deranges the antioxidant defense system and induces histological changes in the epididymis.