Morin hydrate downregulates inflammation-mediated nitric oxide overproduction and potentiates antioxidant mechanism against anticancer drug doxorubicin oxidative hepatorenal toxicity in rats.

Objective: Doxorubicin (DOX) is a frontline antineoplastic drug that kills cancer cells through genotoxic mechanism; however, it induces organ toxicities. This study assayed whether morin hydrate (MOH) could abrogate DOX hepatorenal toxicity in rats. Materials and Methods: There were 4 groups of rats: Control, MOH, DOX and MOH + DOX. Rats were administered MOH (orally, 100 mg/kg bw) for 7 consecutive days, while DOX was injected (40 mg/kg, ip) on the 5th day only. Hepatorenal function markers, and glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) activities were estimated in both organs. Hepatorenal glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) levels were estimated with histopathology. Results: DOX significantly (p<0.05) reduced antioxidant enzyme activities and GSH level, while NO and MDA levels increased (p<0.05) compared to the control. DOX prominently altered hepatorenal indices and induced histopathological alterations. MOH abrogated the DOX hepatorenal toxicity and alleviated the histological lesions in the liver and kidney. Conclusion: MOH restored the indices via antioxidant mechanism and downregulation of NO overproduction in rats.

Synergistic Action of Virgin Coconut Oil and Clomiphene in Reversing Endocrine Dysregulation in Letrozole-Model of Polycystic Ovarian Syndrome in Rats: Role of Nrf2/HMOX-1 Pathway.

Polycystic ovarian syndrome (PCOS) is an endocrine disorder in women's reproductive age. Currently, the pathophysiology of PCOS is unclear, and the limited treatment options are unsatisfactory. Virgin coconut oil (VCO) is functional food oil associated with pharmacological effects in reproductive disorders. Therefore, we aimed to evaluate whether VCO could enhance clomiphene (CLO) therapy against PCOS in female rats. Rats were randomly divided: (1) Control, (2) PCOS model, (3) PCOS + CLO, (4) PCOS + VCO, and (5) PCOS + CLO + VCO. The PCOS was induced via daily letrozole (1 mg/kg, orally) administration for 21 days. After the PCOS induction, CLO, VCO, and CLO + VCO were administered from days 22 to 36. Serum levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estrogen, progesterone, and prolactin were estimated. Polymerase chain reaction gene expression for nuclear factor-erythroid-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), catalase (CAT), glutathione reductase (GSR), LH receptor (LHr), androgen receptor (AR), tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and caspase-3 were analyzed. The letrozole-induced PCOS caused considerable increases in GnRH, LH, prolactin, estrogen, and testosterone, whereas FSH decreased significantly compared to the control. The gene expression of Nrf2, HO-1, CAT, and GSR were markedly diminished, while IL-1ß, TNF-α, caspase-3, AR, and LHr prominently increased compared to control. Interestingly, the CLO and VCO separately exerted anti-inflammatory and endocrine balance effects. However, VCO-enhanced CLO effect in LH, prolactin and testosterone, Nrf2, HO-1, CAT, GSR, and AR. VCO may synergize with CLO to depress hyperandrogenism and oxidative inflammation in PCOS.

Virgin coconut oil reverses behavioral phenotypes of letrozole-model of PCOS in Wistar rats via modulation of NRF2 upregulation.

Objectives: Polycystic ovarian syndrome (PCOS) is an endocrine disorder associated with insulin resistance, hyperandrogenism, and sub-infertility. Virgin coconut oil (VCO) has been reported to have health benefits, such as anti-inflammatory, anti-oxidant, and antiviral properties. This study investigated the effects of dietary VCO supplementation on memory and cognitive impairment in female rats with letrozole induced PCOS. Methods: Thirty female rats were randomly divided into five groups. All rats except controls were treated with letrozole for 21 days to induce PCOS and were subsequently treated for 14 days with 10% VCO, clomiphene (CLO), or VCO + CLO. Three neurobehavioral tests were conducted: elevated plus maze, Y maze, and novel object recognition tests. Results: Our results indicated statistically elevated serum concentrations of sex hormones in rats with PCOS, compared with the control and treated groups. In addition, all treated groups showed significant reversal of the low serum concentrations of catalase and down-regulated gene expression of Nrf2 in the hippocampus seen in the PCOS rats. In addition, gene expression of acetylcholine esterase was up-regulated in PCOS rats, and was statistically reverted in the VCO treated groups. Conclusion: Anxiety-like behavior and impaired short-term memory were observed in PCOS rats; however, VCO supplementation reversed these effects by modulating the gene expression of Nrf2 and AchE.

Diabetic neuropathy is associated with increased pain perception, low serum beta-endorphin and increase insulin resistance among Nigerian cohorts in Ekiti State.

INTRODUCTION: There has been an increase in the global prevalence of diabetic polyneuropathy and research evidence suggests that insulin resistance plays an important role in its development and prognosis. However, there seem to be a dearth of information in understanding the likely interplay between beta endorphin, insulin resistance and pain perception especially in the setting of painful diabetic neuropathy. METHOD: This study recruited 120 volunteers divided into four groups (30 per group): group 1 healthy volunteer (control); group 2 DM type 2 without neuropathy (DM group); group 3 DM type 2 with painful neuropathy (DPN group); group 4 DM type 2 without painful neuropathy (DN). All subjects were evaluated for pain threshold and neuropathy using an ischemia-induced pain model and biothesiometer respectively. Their beta-endorphin, glycated hemoglobin, fasting plasma insulin, and HOMA values were determined and means compared using ANOVA. RESULT: Serum beta-endorphin is significantly reduced in DN and DPN (∗p < 0.001) compared with the control and DM group. Also, DPN and DN patients have significantly increased insulin resistance compared to those without neuropathy (∗p < 0.001; ∗p < 0.0001 respectively). There is a significant positive correlation between the pain threshold and beta-endorphin in all the groups except DN group. The correlation between beta-endorphin and insulin resistance was negative and significant in control and DM groups only. Suggestive that the fact that insulin resistance plays an important role in diabetes polyneuropathy, does not alone explain the chronic pain perception noticed in the DPN patients. CONCLUSION: The present study demonstrates that diabetic neuropathy patients have a poor endogenous opioid peptide system which is associated with increased pain perception and high insulin resistance. However, insulin resistance alone does not explain the chronic pain perception noticed in the DPN patients. Thus, further study is required.