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Oxidative stress (OS) mechanisms are speculated to play a significant role in nickel-induced toxic effects and their carcinogenic potency. Although nickel-induced oxidative damage in somatic tissues is well demonstrated, evidence of the involvement of a similar mechanism(s) in nickel-induced testicular dysfunction and associated genotoxic effects is scarce. Hence, the present study aimed to investigate the nickel-induced OS response in testis and the associated genotoxic implications in vivo. Initially, the toxicity profile of nickel chloride was determined in adult albino mice (CFTSwiss) following administration (intraperitoneal) of single doses. Subsequently, multiple sublethal doses (1.25, 2.5, and 5.0 mol/100 g of body weight per day for 3 days) were used to characterize effects on testicular histoarchitecture, lipid peroxidation (LPO) in testis (homogenates, microsomal or mitochondrial fractions) and epididymal sperm, DNA damage, induction of apoptosis in testis, and incidence of sperm head abnormalities. Although short-term doses of nickel induced only a minimal LPO response, multiple doses elicited a moderate (15% to 30%) increase in LPO in whole homogenates and higher dose-related increases in both mitochondrial (20% to 50%) and microsomal fractions (25% to 60%). This was associated with a significant increase in DNA damage in the testis as evidenced by increased single-strand breaks (fluorimetric analysis of DNA unwinding assay). Further, at higher doses, nickel-induced apoptosis was demonstrable in the testis biochemically. Although caudal sperm counts determined at all sampling weeks showed no alterations, analysis for head abnormalities revealed a nearly 3-to 4-fold increase in the percentage of abnormal sperms among the nickel-treated males during the first 3 weeks. Furthermore, mating of nickel-treated (2.5 mol/100 g of body weight per day for 5 days) males sequentially for a period of 5 weeks with untreated females resulted in a significant increase in male-mediated dominant lethaltype mutations (the frequency of dead implantations) during the first 3 weeks, suggesting a stage-specific effect on postmeiotic germ cells. These findings suggest that testicular toxicity of nickel compounds may be related to enhanced production of reactive oxygen species, probably mediated through oxidative damage to macromolecules, including damage to DNA.

Paraquat (PQ; 1, 1'-dimethyl-4-4'-bipyridinium), an herbicide and model neurotoxicant, is identified to be one of the prime risk factors in Parkinson's disease (PD). In the Drosophila system, PQ is commonly used to measure acquired resistance against oxidative stress (PQ resistance test). Despite this, under acute PQ exposure, data on the oxidative stress response and associated impact on mitochondria among flies is limited. Accordingly, in this study, we measured markers of oxidative stress and mitochondrial dysfunctions among adult male flies (8-10 days old) exposed to varying concentrations of PQ (10, 20, and 40 mM in 5% sucrose solution) employing a conventional filter disc method for 24 h. PQ exposure resulted in significant elevation in the levels of oxidative stress biomarkers (malondialdehyde: 43% increase: hydroperoxide: 32-39% increase), with concomitant enhancement in reduced glutathione and total thiol levels in cytosol. Higher activity of antioxidant enzymes were also evident along with increased free iron levels. Furthermore, PQ exposure caused a concentration-dependent increase in mitochondrial superoxide generation and activity of manganese-superoxide dismutase (Mn-SOD). The activity levels of complex I-III, complex II-III, and Mg+2 adinosine triphosphatase (ATPase) were also decreased significantly. A robust diminution in the activity of succinate dehydrogenase and moderate decline in the citrate synthase activity suggested a specific effect on citric acid cycle enzymes. Collectively, these data suggest that acute PQ exposure causes significant oxidative stress and mitochondrial dysfunction among flies in vivo. It is suggested that in various experimental settings, while conducting the "PQ resistance stress test" incorporation of selected biochemical end points is likely to enhance the quality of the data.

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The primary objective of this investigation was to assess the neuroprotective efficacy of spice active principles namely Eugenol (Eug) and isoeugenol (IE) in an acrylamide (ACR) neuropathy model in rats. In the present study, ACR administration (50 mg/kg bw, i.p. 3 times/week) for 5 weeks to growing rats caused typical symptoms of neuropathy. We found that treatment of ACR rats with spice active principles (10 mg/kg bw, for 5 weeks) caused marked improvement in gait score and responses in a battery of behavioral tests. Terminally, both spice active principles markedly attenuated ACR-induced markers of oxidative stress viz., reactive oxygen species (ROS), malondialdehyde (MDA) and nitric oxide (NO) in sciatic nerve (SN) as well as brain regions (cortex Ct, cerebellum Cb). Treatment with Eug restored the reduced glutathione levels in SN and brain regions. Interestingly, both spice active principles effectively diminished ACR-induced elevation in cytosolic calcium levels and acetylcholinesterase activity in SN and Ct. Further, the diminished activity of ATPase among ACR rats was enhanced in SN and restored in brain regions. Furthermore, Eug treatment significantly offset ACR-induced depletion in dopamine levels in brain regions. Collectively our findings suggest the propensity of these spice active principles to attenuate ACR-induced neuropathy. Further studies are necessary to understand the precise molecular mechanism/s by which these spice active principles attenuate neuropathy. Nevertheless, our data clearly demonstrate the beneficial effects of spice active principles in ACR-induced neuropathy in rats and suggest their possible therapeutic usage as an adjuvant in the management of other forms of neuropathy in humans.

Accumulating evidence suggests that probiotic bacteria play a vital role in modulating various aspects integral to the health and well-being of humans. In the present study, probiotic attributes and the antioxidant, anti-inflammatory and neuromodulatory potential of Enterococcus faecium CFR 3003 were investigated by employing suitable model systems. E. faecium exhibited robust resistance to gastrointestinal stress conditions as it could withstand acid stress at pH 1.5, 2 and 3. The bacterium also survived at a bile salt concentration of 0.45 %, and better tolerance was observed towards pepsin and trypsin. E. faecium produced lactic acid as a major metabolic product, followed by butyric acid. Lyophilized cell-free supernatant (LCS) of E. faecium exhibited significant antioxidant capacity evaluated against 1,1-diphenyl-2-picryl-hydrazyl, ascorbate autooxidation, oxygen radical absorbance and reducing power. Interestingly, E. faecium, Lactobacillus rhamnosus GG MTCC 1408 and LCS showed a significant anti-inflammatory effect by negatively modulating TNF-a production and upregulating IL-10 levels in LPS-stimulated macrophage cell lines. In an in vivo mice model, the propensity of probiotic supplements to modulate endogenous oxidative markers and redox status in brain regions was assessed. Young mice provided with oral supplements (daily for 28 days) of E. faecium and L. rhamnosus exhibited diminished oxidative markers in the brain and enhanced activities of antioxidant enzymes with a concomitant increase in c-aminobutyric acid and dopamine levels. Collectively, our findings clearly suggest the propensity of these bacteria to protect against tissue damage mediated through free radicals and inflammatory cytokines. Although the underlying molecular mechanisms need further studies, it is tempting to speculate that probiotics confer a neuroprotective advantage in vivo against oxidative damage-mediated neurodegenerative conditions.

Oxidative stress is implicated to play a vital role in the pathogenesis of various diabetic complications. While reproductive dysfunction is a well recognized consequence of diabetes mellitus, the underlying mechanisms are poorly understood. The present study aims to obtain insights into the incidence, extent and progression of oxidative impairments in testis and epididymal sperm (ES) in streptozotocin (STZ)-induced diabetic rat during early and progressive phase. Adult rats (CFT-Wistar strain) rendered diabetic by an acute dose of STZ (60 mg/kg bw, i.p.) were examined for induction of hyperglycaemia at 72 h, followed by the assessment of oxidative impairments in testis and ES over a 6-week period. Oxidative damage was ascertained by measuring the malondialdehyde levels, reactive oxygen species (ROS) generation, alterations in antioxidant defences and extent of protein oxidation. STZ induced a significant (2.5-fold) increase in blood glucose levels. In diabetic rats, both testis and ES showed enhanced status of lipid peroxidation measured as increased TBARS and ROS from week 2 onwards. These impairments in testis were consistent, progressive and accompanied by marked alterations in antioxidant defences and elevated protein carbonyls. Varying degree of reduction in the specific activities of antioxidant enzymes was evident in testis and ES, while the activity of glutathione-S-transferase (GST) was significantly elevated. Reduced glutathione (GSH) and vitamin E levels were consistently reduced in testis. Lipid dysmetabolism measured in terms of increased cholesterol, triglycerides and phospholipids was evident only beyond week 2 in diabetic testis. Taken together, these results indicate that the testis and ES are indeed subjected to significant oxidative stress in the STZ-diabetic rat both during early as well as progressive phase. It is hypothesized that oxidative impairments in testis which develop over time may at least in part contribute towards the development of testicular dysfunction eventually leading to testicular degeneration which culminates in reduced fertility during the progressive phase of STZ-induced diabetes in adult rats.

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