Onaolapo, O. J. | Search bioRxiv

bioRxiv2023

Induced-hyperandrogenism in female rats: assessing possible modulation of neurobehavioural and neurotransmitter changes following clomiphene/letrozole intervention

Hyperandrogenism is the excessive production of androgenic hormones resulting in infertility in a number of women. While letrozole and clomiphene citrate have been used to increase chances of achieving pregnancy, their effects on the brain has been scarcely studied. This study examined the effects of clomiphene and letrozole alone or in combination on neurobehavioural and neurochemical changes in female rats exposed to testosterone. Weaned rats were assigned into eight groups of ten each. Animals were grouped as normal control administered vehicle (normal saline) orally at 10 ml/kg or subcutaneously at 2 ml/kg, three groups administered clomiphene (CLOM) at 100 {micro}g/kg, letrozole (LETR) at 5 mg/kg and or a combination of clomiphene and letrozole (CLOM/LETR) orally and saline subcutaneously. There were also four groups Testosterone (Test), Test/CLOM, Test/LETR or Test/CLOM+LETR administered testosterone enantate subcutaneously at 1 mg/100 g. Testosterone or saline was administered from day 1-35, while beginning on day 36, clomiphene, letrozole or saline was administered daily for 10 days. At the end of the dosing period, animals were exposed to different behavioural paradigms. After the behavioural tests, animals were sacrificed, the cerebral cortex was homogenised for the assessment of biochemical assays. The result showed an increase in body weight, food intake, locomotor activity, rearing and self grooming with CLOM, LETR and CLOM/LETR in all treated groups. Decreased spatial working memory and anxiolysis was observed with letrozole and/or clomiphene. Increased oxidative stress, decreased total antioxidant capacity, altered inflammatory cytokines and brain neurotransmitter were observed with letrozole and /or clomiphene. In conclusion, the administration of clomiphene and/or letrozole was associated with significant alterations in brain function, oxidative stress, inflammatory markers and brain neurotransmitter levels.

neuroscience↗

bioRxiv2023

Biflavonoid quercetin protects against cyclophosphamide induced organ toxicities via modulation of inflammatory cytokines, brain neurotransmitters, and astrocyte immunoreactivity

BackgroundQuercetins antioxidative properties make it of potential benefit in many clinical conditions where oxidative stress is implicated in the pathological processes. ObjectivesTo investigate the possible protective effects of quercetin on neurobehaviour, brain oxidative status, markers of inflammation, neurotransmitter balance and astrocyte immunoreactivity in healthy rats administered cyclophosphamide. MethodsSixty rats were randomly assigned into six groups (n=10). Groups A and D served as normal and cyclophosphamide control respectively and were fed standard rat chow, groups B and E were fed quercetin supplemented diet (100 mg/kg of feed), while those in groups C and F were fed quercetin supplemented diet at 200 mg/kg of feed. Animals in group A-C also received intraperitoneal normal saline on days 1 and 2, while those in groups D-F got intraperitoneal cyclophosphamide (150 mg/kg/day on days 1 and 2). Standard diet and quercetin supplemented diet were administered daily for 21 days. At the end of the experimental period, behavioural tests were carried out, following which animals were sacrificed and blood taken for the assessment of biochemical parameters. Organs were either homogenised or processed for histological study. ResultsQuercetin mitigated CYP-induced weight loss and reduction in food consumption. It also improved total antioxidant capacity while reducing CYP-induced lipid peroxidation and biochemical markers of impaired liver function. A reduction in CYP-induced increase in urea and creatinine was also observed. Interleukin-10 increased, while the CYP-induced increase in interleukin-1 beta and TNF- were also mitigated following quercetin administration. Open field exploratory activities and grooming increased with CYP and the lowest dose of quercetin. The anxiolytic effects of quercetin was demonstrable in the elevated plus maze; while its memory-enhancing effects were seen in the Y-maze and radial-arm maze. Finally, quercetin improved acetylcholine/dopamine levels and brain-derived neurotropic factor, while reducing serotonin levels and astrocyte immunoreactivity. ConclusionThe results show quercetins ability to protect against CYP-induced changes in rats. They also highlight the possible use of quercetin as a possible adjunct in cancer chemotherapy-induced tissue damage. However, further research will be needed to delineate its exact role in cancer chemotherapy.

pharmacology and toxicology↗