Diosmin protects the testicles from doxorubicin-induced damage by increasing steroidogenesis and suppressing oxido-inflammation and apoptotic mediators.

BACKGROUND: Cancer chemotherapy with doxorubicin (DOX) has been linked to serious testicular damage and spermatotoxicity due to the induction of oxidative stress, inflammation, and apoptosis. Thus, the current study was carried out to assess the potential ameliorative impact of diosmin, an antioxidant drug, against DOX-mediated spermatoxicity and testicular injury in rats. MATERIAL AND METHODS: In the experimental protocol, rats were grouped into 4: Group 1 received vehicle and saline for 8 weeks while group 2 received diosmin and saline concomitantly for 8 weeks. Group 3 was given 3 mg/kg intraperitoneal DOX once every 7 days for 8 weeks. Group 4 was given 40 mg/kg of diosmin orally for 56 days followed by DOX diosmin administration after one hour. After 56 days of treatment, sperm quality, hormonal testing, biochemical parameters, and histological alterations in the testes were evaluated. RESULTS: DOX-induced reduce spermatogenic function, testicular 3- and 17ß-Hydroxysteroid dehydrogenases, and serum follicle stimulating hormone, luteinizing hormone, and testosterone. It also enhanced inflammation, testicular oxidative damage, and apoptosis. The histopathologic examinations corroborated the biochemical results obtained. Significantly, diosmin treatment reduced DOX-induced injury, as evidenced by restored testicular architecture, increased steroidogenesis, preservation of spermatogenesis, suppression of oxide-inflammatory response, and apoptosis. CONCLUSION: It was found that through diosmin antioxidant, anti-apoptotic, and anti-oxido-inflammatory it presents a possible therapeutic alternative for protecting testicular tissue against DOX's harmful effects.

D-ribose-L-cysteine exhibits restorative neurobehavioral functions through modulation of neurochemical activities and inhibition oxido-inflammatory perturbations in rats exposed to polychlorinated biphenyl.

Polychlorinated biphenyl (PCB) is potentially harmful environmental toxicant causing cognitive decline with depressive features. PCB-induced behavioral deficits are associated with neurochemical dysfunctions, immune changes, and oxidative stress. This study investigated the neuroprotective effects of D-ribose-L-cysteine (DRLC), a neuroprotective precursor element of glutathione on PCB-induced neurobehavioral impairments. Following the initial 15 days of PCB (2 mg/kg) exposure to rats, DRLC (50 mg/kg) was given orally for an additional 15 days, from days 16 to 30. Animals were assessed for behavioral effect such as changes in locomotion, cognition, and depression. Oxidative/nitrergic stress markers; antioxidant regulatory proteins paraoxonase-1 (PON-1), heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nfr2), NADPH oxidase-1 (NOX-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and neuroinflammation (NF-kß, and TNF-α); and neurochemical metabolizing enzymes (acetylcholinesterase (AChE), monoamine oxidase-A and -B (MAO-A, MAO-B)) were carried out. The PCB-induced decline in locomotion, cognitive performance, and depressive-like features were reversed by DRLC. More specifically, PCB-induced oxidative and nitrergic stress, typified by reduced levels GSH, CAT, and SOD, accompanied by elevated MDA and nitrite were attenuated by DRLC. Additionally, DRLC restored the neuroinflammatory milieu indicated by decreased NF-kß and TNF-α levels toward normal. Hyperactivities of AChE, MAO-A, MAO-B, PON-1, and NOX-1 levels as well as Nfr2, NQO1, and PON-1 due to PCB exposure were mitigated by DLRC. Our results suggest DRLC as a prospective neurotherapeutic agent against PCB-induced neurobehavioral impairments such as cognitive deficit and depressive-like feature through antioxidative and anti-nitrergic stress, anti-neuroinflammation, inhibition of brain metabolizing enzymes, and normalization of neurochemical homeostasis.

Possible mechanisms involved in the testicular-protective property of quercetin in rats exposed to endosulfan toxicity.

The study investigated the effects of quercetin and putative mechanisms involved against endosulfan-testicular impairments in rats. Rats were allotted into five treatment groups (n = 5). Groups 1-2 had normal saline and maize oil (vehicle) (10 mL/kg), group 3 received quercetin (20 mg/kg), 4-5 had endosulfan (5 mg/kg, p.o) orally for 28 days. However, from days 14-28, group 4 received an additional dose of vehicle (10 mL/kg, p.o./day), while group 5 received quercetin (20 mg/kg, p.o./day). Thereafter, blood samples and testes were harvested for markers of cholinergic, hormonal and testicular oxido-nitrergic, inflammatory, apoptosis and proton pump ATPase activities. Also, testicular histopathological changes were also evaluated alongside with germ cell count, testicular injury and spermatogenesis score. Quercetin increased testicular/body weights and spermatogenesis, androgenic hormones (follicle stimulating hormones, FSH; luteinizing hormone, LH; testosterone), acetylcholinesterase levels and attenuated altered membrane integrity, DNA fragmentation, increased caspases-3 levels in rats exposed to endosulfan. Moreover, quercetin increased testicular B-cell lymphoma-2 (Bcl-2), Bcl-2 associated x-protein (Bax) and proton pump adenosine trisphosphate (ATPase) and sialic acid levels. Of note, quercetin reversed endosulfan-mediated increased malondialdehyde, nitrite, peroxynitrite formation, 8-hydroxy-2'-deoxyguanosine and lowered antioxidant enzymes in the testes. The increased levels of testicular myeloperoxidase (MPO), tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1ß) by endosulfan were also reduced by quercetin administration. Additionally, quercetin attenuate endosulfan-induced testicular histopathological changes of rats. Our findings showed that quercetin significantly inhibited endosulfan-induced testicular damage and altered spermatogenesis through inhibition of oxido-nitrergic pathway, inflammatory mediators, apoptosis, acetylcholinesterase activity and enhancement of testicular hormones and improvement in testicular ATPase activity.

Repeated endosulfan exposure induces changes in neurochemicals, decreases ATPase transmembrane ionic-pumps, and increased oxidative/nitrosative stress in the brains of rats: Reversal by quercetin.

Neurochemical and ATPase deregulations play important role in toxicant-induced neurodegeneration. Previous studies have shown that loss of ATPase ionic-pumps alters neurochemical balance via increased ammonia, oxidative and nitrosative stress. Thus, this study investigated the ameliorative potentials of quercetin on neurochemical, ATPase changes, hyperammonemia and oxidative/nitrosative status in the brains of Wistar rats exposed to endosulfan, a known toxic environmental pesticide that is casually used in many developing countries. Adult rats were divided into five treatment groups (n = 5). Groups 1-2 received normal saline and corn oil (vehicle) (10 mL/kg/day), group 3 received quercetin (20 mg/kg/day) orally for 28 days consecutively. However, animals in groups 4-5 were given endosulfan (5 mg/kg/day, p.o) for 28 days. But, from the 14th to 28th day, group 4 additionally received vehicle (10 mL/kg/day, p.o.), while group 5 was treated with quercetin (20 mg/kg/day, p.o.). Thereafter, brain levels of neurochemicals, ATPase activities, ammonia and oxidative/nitrosative stress were investigated by employing standardized biochemical assay protocols. Quercetin increased endosulfan-induced decreased levels of norepinephrine, dopamine, GABA, and decreased elevated concentrations of glutamate and serotonin. Quercetin normalized the increased levels of acetylcholinesterase and ammonia. Furthermore, quercetin significantly reversed the decrease in Na+/K+, Ca2+, Mg2+-ATPase activities induced by endosulfan. Also, quercetin increased superoxide dismutase, catalase and glutathione peroxidase activities, and reduced nitrite and peroxynitrite levels in brains of rats. These findings further provide evidence of the ameliorative potential of quercetin against endosulfan-induced neurotoxicity via attenuation of neurochemical, ATPase changes, and inhibition of acetylcholinesterase activity, ammonia release and oxidative/nitrosative stress in rat brains.