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.

d-ribose- l-cysteine abrogates testicular maladaptive responses induced by polychlorinated bisphenol intoxication in rats via activation of the mTOR signaling pathway mediating inhibition of apoptosis, inflammation, and oxidonitrergic flux.

Male reproductive maladaptive responses are becoming a global health concern and also a social issue. Polychlorinated biphenyls (PCBs) are a member of halogenated aromatic environmental pollutants with diverse environmental matrices. This study was conducted to explore the mechanisms of PCBs-induced testicular maladaptive responses and the potential reversal effects of d-ribose- l-cysteine (DRLC) on testicular injury induced by administration of PCBs (2 mg/kg) for 30 days. DRLC (50 mg/kg) was administered orally for 15 days starting from Days 16 to 30 after the initial 15 days of treatment with PCB. All assays were carried out using established protocols. Administration of DRLC at 50 mg/kg after treatment with PCBs enhances body and testicular weights, gonadotropins (luteinizing hormone and follicle-stimulating hormone), testosterone and poor sperm quality. DRLC also reduced testicular injury score, improved spermatogenesis scoring, reduced oxidative stress biomarkers (malondialdehyde), as well as restored the reduced activities of antioxidant enzymes (glutathione peroxidase, superoxide dismutase, and catalase) and decreases pro-inflammatory response (tumor necrosis factor-alpha and NO). More so, DRLC treatment abrogates testicular DNA fragmentation and downregulated p53 and caspase 3 activities and upregulated the concentration of autophagy-related protein (mammalian target of rapamycin [mTOR] and Atg7). DRLC abates testicular deficit induced by PCBs intoxicated rats via activation of the mTOR signaling pathway mediating inhibition of apoptosis, Inflammation and oxidative flux.

Kolaviron abates busulfan-induced episodic memory deficit and testicular dysfunction in rats: The implications for neuroendopathobiological changes during chemotherapy.

Busulfan is a popular antileukemia chemotherapeutic alkylating agent widely known to induce variety of serious adverse effects including chemobrain-related cognitive impairments and dysfunction in male reproductive system. Whether kolaviron, a neuro- and repro-active compound obtained from Garcinia kola, with neuroprotective and reproductive-promoting activities, mitigates busulfan-induced cognitive and male reproductive impairments remain unknown. Hence, we investigated the reversal effects of kolaviron on busulfan-induced episodic memory deficit and testicular dysfunction, and its underlying mechanisms in male rats. In the treatment-protocol, rats in groups 1 and 2 received saline (10 mL/kg/p.o./day) and DMSO (10 mL/kg/p.o./day) respectively, group 3 was given kolaviron (200 mg/kg/p.o./day), group 4 received busulfan (50 mg/kg/p.o./day) and group 5 was pretreated with busulfan (50 mg/kg/p.o./day) consecutively for 56 days prior to kolaviron treatment (200 mg/kg/p.o./day) from days 29-56. Episodic memory deficit was assessed using passive avoidance task (PAT). Following euthanization, blood samples, epididymal sperm, testes and brain were harvested and hormonal and neurochemical contents and their metabolizing enzymes were assayed. Kolaviron reversed busulfan-induced episodic cognitive deficit in the PAT. The reduced serotonin, dopamine, noradrenaline concentrations, elevated glutamate levels, acetylcholinesterase, monoamine oxidase-A and B activities were normalized by kolaviron. Kolaviron also reversed the busulfan-induced decreased testicular/body weights and spermatogenesis. Kolaviron abated busulfan-induced changes in androgenic hormones (testosterone, FSH, LH), dehydrogenase enzymes (3ß-HSD and 17ß-HSD), altered sperm-chromatin, sperm-membrane integrity and sperm-acrosomal reaction and capacitation impairments. Our findings suggest that kolaviron could mitigate busulfan-induced episodic memory deficit and dysfunction in male reproductive system via neurochemical modulations and increase testicular androgenic hormones/enzymes in rats.

Prevention and reversal of chlorpromazine induced testicular dysfunction in rats by synergistic testicle-active flavonoids, taurine and coenzyme-10.

Evidences have shown that alterations in testicular dehydrogenase and ionic-ATPase activities have important implications in spermatogenesis and sperm capacitation, a penultimate biochemical change required for fertilization. Previous studies have revealed that taurine and coenzyme-Q10 (COQ-10), which are synergistic testicle-active bioflavonoids, with proven gonadotropin-enhancing properties reduce testicular damage in rats. Hence, this study investigated the effects of taurine and COQ-10 or their combination alone, and in the preventive and reversal of chlorpromazine-induced inhibition of testicular dehydrogenase enzymes, electrogenic pumps, sperm capacitation and acrosomal-reaction in male Wister rats. In the drug-treatment alone or preventive-protocol, rats received oral treatment of saline (10 mL/kg), taurine (150 mg/kg/day), COQ-10 (10 mg/kg/day) or both alone repeatedly for 56 days, or in combination with chlorpromazine (30 mg/kg/p.o./day) from days 29-56. In the reversal-protocol, the animals received chlorpromazine for 56 days prior to saline, taurine, COQ-10 or the combination from days 29-56. Thereafter, spermatogenesis (sperm count, viability, motility and morphology), testicular dehydrogenase [3beta-hydroxysteroid dehydrogenase (3ß-HSD), 17beta-hydroxysteroid dehydrogenase (17ß-HSD), glucose-6-phosphate dehydrogenase (G6PDH), lactate dehydrogenase-X (LDH-X)], ATPase (Na+/K+, Ca2+, Mg2+, H+) activities, sperm capacitation and acrosomal reaction were evaluated. Taurine and COQ-10 or their combination increased spermatogenesis, testicular 3ß-HSD, 17ß-HSD, G6PDH and LDH-X enzymes of naïve and chlorpromazine-treated rats. Both taurine and COQ-10 increased Na+/K+, Ca2+, Mg2+ and H+-ATPase activities. Also, taurine and COQ-10 or their combination prevented and reversed chlorpromazine-induced inhibition of sperm capacitation and acrosomal-reaction. The study showed that taurine and COQ-10 prevent and reverse chlorpromazine-induced inhibition of spermatogenesis, epididymal sperm capacitation and acrosomal reaction in rats through increased testicular dehydrogenases and electrogenic pump activities.

Taurine and coenzyme Q10 synergistically prevent and reverse chlorpromazine-induced psycho-neuroendocrine changes and cataleptic behavior in rats.

Over the years, mounting evidences have suggested a strong association between chronic chlorpromazine therapy, a popular first-generation antipsychotic drug, and psycho-neuroendocrine changes. In this study, we aim to examine whether treatment with taurine and coenzyme Q10 (COQ-10), compounds with steroidogenic-gonadotropin hormone-enhancing properties, can attenuate the negative impacts of chlorpromazine on steroidogenic, gonadotropin, thyroid and HPA-axis hormones, dopamine levels, catalepsy behavior and neuronal cells of the hypothalamus and pituitary gland in the preventive and reversal treatments in male Wister rats. In the drug treatment alone or preventive protocol, rats received oral administration of saline (10 mL/kg), taurine (150 mg/kg/day), COQ-10 (10 mg/kg/day), or both (taurine + COQ-10/day) alone for 56 consecutive days, or in combination with oral chlorpromazine (30 mg/kg/day) treatment from days 29 to 56. In the reversal protocol, the animals received chlorpromazine or saline for 56 days prior to taurine, COQ-10, or the combination from days 29 to 56. Thereafter, serum prolactin, steroidogenic (testosterone, estrogen, progesterone), gonadotropin (luteinizing hormone, LH, follicle-stimulating hormone, FSH), thyroid (thyrotropin-stimulating hormone, tetraiodothyronine, triiodothyronine) hormones, corticosterone, brain dopamine levels and cataleptic behavior were investigated. The histopathological features of the hypothalamus and pituitary gland were also evaluated. Taurine, COQ-10, or their combination prevented and reversed chlorpromazine-induced hyperprolactinemia, decrease in FSH, LH, testosterone, progesterone and dopamine concentrations, as well as the increase in estrogen levels. Taurine and COQ-10 reduced the changes in thyroid hormones, corticosterone release, histological distortions of the hypothalamus and the pituitary gland of chlorpromazine-treated rats. Taurine and COQ-10 attenuated chlorpromazine-induced catalepsy. The study showed that taurine and COQ-10 prevented and reversed chlorpromazine-induced changes in reproductive, thyroid hormones, dopamine level, corticosterone release, neurodegenerations, and cataleptic behavior in rats.