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The COVID-19 pandemic has spurred an unprecedented movement to develop safe and effective vaccines against the SARS-CoV-2 virus to immunize the global population. The first set of vaccine candidates that received emergency use authorization targeted the spike (S) glycoprotein of the SARS-CoV-2 virus that enables virus entry into cells via the receptor binding domain (RBD). Recently, multiple variants of SARS-CoV-2 have emerged with mutations in S protein and the ability to evade neutralizing antibodies in vaccinated individuals. We have developed a dual RBD and nucleocapsid (N) subunit protein vaccine candidate named RelCoVax® through heterologous expression in mammalian cells (RBD) and E. coli (N). The RelCoVax® formulation containing a combination of aluminum hydroxide (alum) and a synthetic CpG oligonucleotide as adjuvants elicited high antibody titers against RBD and N proteins in mice after a prime and boost dose regimen administered 2 weeks apart. The vaccine also stimulated cellular immune responses with a potential Th1 bias as evidenced by increased IFN-γ release by splenocytes from immunized mice upon antigen exposure particularly N protein. Finally, the serum of mice immunized with RelCoVax® demonstrated the ability to neutralize two different SARS-CoV-2 viral strains in vitro including the Delta strain that has become dominant in many regions of the world and can evade vaccine induced neutralizing antibodies. These results warrant further evaluation of RelCoVax® through advanced studies and contribute towards enhancing our understanding of multicomponent subunit vaccine candidates against SARS-CoV-2.

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.

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.

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.

This article focuses on the effects of prenatal exposure to genistein on the mother, her pregnancy and reproductive functions of the male progeny, since these issues have ethological relevance in both animals and humans. Pregnant Wistar rats received i.p. injections of genistein at a dose level of 2, 20 or 100 mg/kg body weight daily from 12th to 19th day of gestation. Male pups from control and genistein exposed animals were weaned and allowed to develop until 100 days of age; however, when they were 90 days old, twelve males from each group were cohabited with untreated 90-day old females for 8 days. Results revealed a significant decrease in indices of reproductive organs in adult male rats exposed to genistein during embryonic development. Dose dependent reduction was observed in daily sperm production and epididymal sperm density and quality in genistein treated rats. Significant decrease was observed in the activity levels of 3β- and 17β-hydroxysteroid dehydrogenases in testis of experimental rats with a decline in plasma testosterone levels. Histological examination of testis of genistein treated rats indicated deterioration in testicular architecture. In the fertility study, the mean number of implantations and live fetuses per dam mated with 100 mg genistein exposed males was reduced.

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.

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.

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.

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.

This study reports the protective effects of selenium on fluoride induced alterations in the activities of pro-oxidative (xanthine oxidase (XOD), lipid peroxidation (LPO) free radical scavenging, [catalase, superoxide dismutase (SOD), glutathione-s-transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione) and metabolic (glucose-6-phosphate dehydrogenase, alanine amino transferase (ALAT), aspartate aminotransferase (AAT), creatine phosphokinase (CPK), acid phosphatase (AP), alkaline phosphatase (ALP)] enzymes along with fluoride and selenium levels in brain of mice. Animals were divided into control, NaF treated group (20 mg kg(-1) body wt.(-1) intraperitonial) and Selenium+NaF treated group (sodium selenite, 5 microg of selenium/0.2 ml distilled water kg(-1) body wt.(-1) day) and were maintained for 14 days on respective treatments. The decreased bodyweight (-11.35%) as well as organosomatic index (-15.1%) of brain in NaF group were recovered in treatment of selenium along with NaF. The increased accumulation of fluoride (32.1%) in brain observed in NaF treated group compared to control was diminished in selenium+NaF treated group. Selenium levels (3.03%) increased in selenium+NaF treated group in compared to decrement in NaF treatment. The SOD (-16.6%), Catalase (-21.5%), GST(-13.72%), GPX (-19.16%), GR (-44.97%) activities and Glutathione (-23%) content in NaF treated group were decreased significantly compared to controls, which were significantly (p0.01) recovered in selenium+NaF group. Increased XOD (10.85%) and LPO (8.61%) levels observed in brain of NaF treated mice were reversed with selenium treatment. Glucose-6-phosphate dehydrogenase (-46.98%), ALAT (-10.44%), AAT (-10.21%), CPK (-27.98%) were decreased and alkaline phosphatase (10.6%), acid phosphatase (24.09%) increased in brain of mice after administration of NaF. All metabolic enzymes were significantly (p0.01) reversed after administration of selenium to the NaF treated group. Thus, the adverse effects of NaF on oxidative and metabolic enzymes of brain were reversible with ameliorative action of selenium supplementation. As evident in this study the antioxidative nature of selenium coupled with its reversal effect on metabolic enzymes in brain of mice treated with fluoride suggests its use as antidote agent against fluorosis.

This study reports the effects of low level developmental Pb exposure on specific brain regions like hippocampus, cerebellum and cerebral hemispheres of antioxidant enzyme activities. Wistar dams were exposed to 50 ppm, 100 ppm and 500 ppm of Pb acetate in drinking water during pregnancy and lactation (gestation day 6 through PND 21 (post natal day) and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GR) were determined in the hippocampus, cerebellum and cerebral hemispheres of pups during treatment period (PND 7, 14, and 21 days) and also during withdrawl period (PND 35, 45, 60 and 90 days). During treatment period, SOD activity significantly (p0.05) decreased in all regions of all the treated groups with maximum decrease in 500 ppm treated group of 21 days, while GSH-Px and GR activities increased with maximum increase in 21 days aged 500 ppm group. During withdrawl period, the activities of all enzymes were significantly (p0.05) reversed. Thus the perinatal exposure of dams to variable dosages of low level lead results in characteristic neurochemical alterations in rat brain regions due to impaired antioxidants function.