Polycyclic aromatic hydrocarbons in a polyherbal drug: human health exposure-associated risk assessment study.

PAHs are pervasive pollutants known to bioaccumulate in environmental matrices, plants, and humans. Dr. Iguedo Goko Cleanser® is a polyherbal drug with unsubstantiated claims to treat various diseases in sub-Saharan Africa. PAHs were measured following EPA-16 PAHs guidelines using Gas Chromatography (Agilent-6890N, USA). The drug's exposure-associated public health concerns was determined using suitable mathematical paradigms. PAHs present were acenaphthene (2.74 × 10-2), pyrene (2.7598 × 10-2), and chrysene (5.1277 × 10-2) ppm. Dietary intake of chrysene, acenaphthene and pyrene for adults, and children ranged from 2.466-4.615 × 10-3 and 1.215-2.308 × 10-3 ppm/mg/kg, respectively. B[α]Peq, EDB[α]Peq, and incremental lifetime cancer risk were determined to be 5.6777 × 10-4, 5.109912 × 10-5 and 5.3289 × 10-12, respectively. Our results suggest a high risk of non-carcinogenic adverse health effects, especially on chronic exposure among adolescents and adults, necessitating caution and/or avoidance of its chronic use. Therefore, policy formulation and implementation as regards the safety of plant-based remedies and allied products before their distribution among end-users must be ensured.

Toxicological evaluation of a polyherbal formulation on testicular function and gonadal histomorphology in exposed Wistar rats.

Introduction: Dr Iguedo Goko Cleanser® is a herbal formulation (HF) widely marketed in southern Nigeria and purported to be very efficacious for the management of various diseases including giardiasis, toilet infections, hypertension, diabetes, ulcer, impotence, low libido, low sperm count amongst others. Medicinal plants reportedly produce an array of adverse reactions capable of inducing harmful conditions, including death. Aim: This study evaluated the subchronic toxicity concern of HF on testicular function and gonadal histoarchitecture in Wistar rats. Methods: Thirty Wistar rats of both sexes were randomly divided into six groups (5/group) and were orally administered HF for 60 days. The control groups received 5 mL/kg of distilled water; the treatment groups were administered 476.24 and 158.75 mg/kg body weight of HF each for both male and female rats. Using standard procedures, semen analysis was done for all male rats. Animals were anaesthetised and sacrificed on the 62nd day; the gonads were eviscerated, weighed and fixed in 10% buffered formalin for histopathological examinations. Results: Significant (p < 0.05) increase in sperm count relative to control as well as spermatotoxic effects were observed in male rats. Histologically, the ovary presented some degrees of pathologies: cloggy appearing ovarian cortex with a display of a tumour-like cortical area, scantily displayed primordial follicles, haemorrhagic blood vessels, atretic secondary follicle, and eroding granulosa cells amongst others. Testicular histopathology showed abnormal seminiferous tubules' histoarchitecture, degenerated spermatids, distorted spermatogenic cells' orientation, and displaced spermatids into the luminal space. Conclusion: Herbal drugs are usually regarded to be completely safe due to their natural sources, however, this study discovered exposure-related toxic effects of Dr Iguedo Goko Cleanser® on testicular function and gonadal histomorphology. The findings recommend extreme caution with chronic use and avoidance whenever possible.

Modulation of GABA by sodium butyrate ameliorates hypothalamic inflammation in experimental model of PCOS.

Polycystic ovarian syndrome (PCOS) is a known endocrine disorder that has affected many women of childbearing age, and is accompanied by various neurodegenerative conditions. Hence, this study investigates the impact of butyrate in reversing hypothalamic-related disorder, possibly through γ aminobutyric acid (GABA) in a rat model of PCOS. Eight-week-old female Wistar rats were allotted into four groups (n = 5), which include control, butyrate, letrozole, and letrozole + butyrate groups. PCOS was induced by administering 1 mg/kg of letrozole (oral gavage) for 21 days. After confirmation of PCOS, 200 mg/kg of butyrate (oral gavage) was administered for 6 weeks. Rats with PCOS were characterized by elevated levels of plasma insulin and testosterone. Increases in plasma and hypothalamic triglyceride levels, inflammatory biomarker (SDF-1), apoptotic marker (caspase-6), and decreased plasma GnRH were observed. Additionally, a decrease in hypothalamic GABA was revealed. Nevertheless, the administration of butyrate attenuated these alterations. The present study suggests that butyrate ameliorates hypothalamic inflammation in an experimental model of PCOS, a beneficial effect that is accompanied by enhanced GABA production.

Mineralocorticoid receptor blockade attenuates hyperandrogenic metabolic dysregulation in letrozole-induced PCOS rat model.

Purpose: Polycystic ovarian syndrome (PCOS) is a metabolic syndrome associated with mineralocorticoid receptor (MR) activation, which causes infertility in women of reproductive age. Spironolactone (SPL) is a MR blocker with inconclusive effect in the treatment of PCOS. Therefore, the present study hypothesized that low dose SPL would ameliorate metabolic dysfunction associated with PCOS. Methods: Female Wistar rats (8-week-old) were divided into 3 groups namely: Control, SPL, Letrozole (LET)-treated and LET + SPL-treated groups. The control group was given vehicle (distilled water), SPL-treated group received 0.25 mg/kg, LET-treated group received 1 mg/kg of LET and LET + SPL-treated group received a combination of LET and SPL. The administrations were done by oral gavage for 21 days uninterruptedly. Biochemical parameters such as lipid profile, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), γ-glutamyl transferase (GGT), lactate dehydrogenase (LDH), testosterone, 17-ß estradiol and glutathione peroxidase (GPx) were determined with appropriate assay methods. Results: Letrozole-treated group had a significant increase in ovarian weight, plasma and ovarian triglycerides, MDA/TNF-α, GGT/LDH and plasma testosterone while it decreased plasma 17-ß estradiol and plasma/ovarian high-density lipoproteins and GPx when compared with control group. In addition, histomorphological changes were observed in LET-treated group compared with control group. Nevertheless, administration of low dose SPL attenuated these perturbations. Conclusion: The present study therefore demonstrates that inhibition of mineralocorticoid receptor by low dose SPL ameliorates hyperandrogenic metabolic dysfunction in a rat model of PCOS. Therefore, low dose SPL is hereby suggested as a promising therapeutic agent in the management of PCOS.

Short chain fatty acid, acetate restores ovarian function in experimentally induced PCOS rat model.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is pathogenically characterized with hyperandrogenism and metabolic alterations, which often result in ovarian changes and infertility in women of reproductive age. Epigenetic changes have been linked to the development of PCOS. However, the involvement of epigenetic regulator, histone deacetylase (HDAC) in PCOS-driven ovarian dysfunction is not clear. Howbeit, the present study hypothesized that acetate, an HDAC inhibitor (HDACi) would protect against ovarian dysfunction in experimentally induced PCOS. MATERIALS AND METHODS: Female Wistar rats weighing 120-150 g were randomly divided into four groups (n = 6). The groups received vehicle, sodium acetate (200 mg/kg), letrozole (1 mg/kg) and letrozole with acetate by oral gavage respectively. The administrations were done daily for 21 days. RESULTS: The rat model of PCOS had increased body weight and ovarian weight, 1-hr postload glucose and plasma insulin, testosterone and LH/FSH ratio as well as reduced insulin sensitivity and plasma 17-ß estradiol and sex hormone binding globulin. This model of PCOS in addition showed a significant increase in plasma and ovarian triglyceride, total cholesterol, TNF-α and HDAC, and ovarian malondialdehyde as well as a significant reduction in ovarian glutathione peroxidase/reduced glutathione and NrF2 with the histology of ovarian tissues showing disrupted morphology with significant increase in the number of degenerated follicles compared with control group. These alterations were however attenuated when treated with HDACi, acetate. CONCLUSION: Altogether, the present results suggest that acetate protects ovarian function with evidence of normal growing follicles and enhanced circulating 17-ß estradiol by inhibition of HDAC.

Low-dose spironolactone abates cardio-renal disorder by reduction of BAX/inflammasome expression in experimentally induced polycystic ovarian syndrome rat model.

The impact of low-dose spironolactone (LSPL) on polycystic ovarian syndrome (PCOS)-associated cardio-renal disorder is unknown. Therefore, the present study hypothesized that LSPL would ameliorate cardio-renal disorders in experimental PCOS animals. Eight-week-old female Wistar rats were allotted into three groups. The control group received vehicle (distilled water; per os (p.o.)), the letrozole (LET)-treated group designated as PCOS group received LET (1 mg/kg; p.o.), and PCOS+LSPL received LET and LSPL (0.25 mg/kg, p.o.). The treatment was done once daily for 21 days uninterrupted. The experimental PCOS rats were characterized with insulin resistance, as well as elevated testosterone and luteinizing hormone/follicle-stimulating hormone, with a significant increase in cardiac and renal lipid profile, oxidative stress, inflammatory biomarkers (nuclear factor-κB and tumor necrosis factor-α), lactate dehydrogenase and lactate content and decrease in cardiac and renal antioxidant system (glutathione peroxidase and reduced glutathione) compared with the control rats. In addition, immunohistochemical assessment of cardiac and renal tissue showed significant expression of inflammasome and B-cell lymphoma-2 associated X-protein (BAX) in animals with PCOS. Nevertheless, these perturbations were attenuated following the administration of LSPL. Collectively, the present results suggest that LSPL attenuates PCOS-associated cardio-renal disorders by reduction of oxidative stress and BAX/inflammasome expression.

Melatonin supplementation preserves testicular function by attenuating lactate production and oxidative stress in high fat diet-induced obese rat model.

Metabolic syndrome, including obesity has been documented as a critical factor in male reproductive dysfunction with subsequent reduction in male fertility. The therapeutic potential of melatonin has been demonstrated against oxidative stress-induced pathologies. Therefore, the present study investigated the effects of melatonin on testicular dysfunction associated with high fat diet (FD)-induced obese rat model, and the possible involvement of peroxisome proliferator-activated receptor-γ (PPAR-γ). Adult male Wistar rats (n = 6/group) were used: control group received vehicle (normal saline), obese group received 40% FD, melatonin-treated group received melatonin (4 mg/kg), and obese plus melatonin group received melatonin and 40% FD and the treatment lasted for 12 weeks. High fat diet caused increased body weight and testicular triglyceride, total cholesterol, malondialdehyde, γ-glutamyl transferase, lactate production and lactate/pyruvate ratio as well as decreased glutathione/glutathione peroxidase, nitric oxide and PPAR-γ and circulating testosterone. Nevertheless, all these alterations were attenuated when supplemented with melatonin. Taken together, these results demonstrates that FD-induced obesity causes testicular dysfunction. In addition, the results suggest that melatonin supplementation protects against obesity-associated testicular dysfunction and this effect is accompanied by upregulation of PPAR-γ.

Protective role of melatonin against adipose-hepatic metabolic comorbidities in experimentally induced obese rat model.

BACKGROUND: Adipose and hepatic metabolic dysfunctions are critical comorbidities that also aggravate insulin resistance in obese individuals. Melatonin is a low-cost agent and previous studies suggest that its use may promote metabolic health. However, its effects on some comorbidities associated with obesity are unknown. Herein, we investigated the hypothesis that melatonin supplementation would attenuate adipose-hepatic metabolic dysfunction in high fat diet (HFD)-induced obesity in male Wistar rats. MATERIALS AND METHODS: Twenty-four adult male Wistar rats (n = 6/group) were used: Control group received vehicle (normal saline), obese group received 40% high fat diet, melatonin-treated group received 4 mg/kg of melatonin, and obese plus melatonin group received 40% HFD and melatonin. The treatment lasted for 12 weeks. RESULTS: HFD caused increased food intake, body weight, insulin level, insulin resistance and plasma and liver lipid but decreased adipose lipid. In addition, HFD also increased plasma, adipose and liver malondialdehyde, IL-6, uric acid and decreased Glucose-6-phosphate dehydrogenase, glutathione, nitric oxide and circulating obestatin concentration. However, these deleterious effects except food intake were attenuated when supplemented with melatonin. CONCLUSION: Taken together, the present results indicate that HFD exposure causes adipose-hepatic metabolic disturbance in obese animals, which are accompanied by oxidative stress and inflammation. In addition, the present results suggest that melatonin supplementation attenuates adipose-hepatic metabolic dysfunction, accompanying obesity by suppression of oxidative stress/inflammation-dependent mechanism and increasing circulating obestatin.

Polyphenol-rich extract of Ocimum gratissimum leaves prevented toxic effects of cyclophosphamide on the kidney function of Wistar rats.

BACKGROUND: Cyclophosphamide (CP) is one of the potent and low cost chemotherapy used in clinical setting against a variety of tumors. However, its association with nephrotoxicity limits its therapeutic use. Ocimum gratissimum leaf is a medicinal plant with numerous pharmacological and therapeutic efficacies, such as antioxidant, anti-inflammation, and anti-apoptotic properties. METHODS: The present study was designed to evaluate the protective effect of Ocimum gratissimum (OG) against CP-induced kidney dysfunction in rats. Rats were pre-treated with 400 mg/kg b.w. of leave extract of Ocimum gratissimum (Ocimum G.) for 4 days and then 50 mg/kg b.w. of CP was co-administered from day 5 to day 7 along with Ocimum G. Markers of renal function and oxidative stress, food and water intake, electrolytes, aldosterone, leukocytes infiltration, inflammation and histopathological alteration were evaluated. RESULTS: Obvious renal inflammation and kidney injuries were observed in CP treated groups. However, administration of leave extract of Ocimum G. prevented oxidative stress, kidney injuries, attenuated inflammation, increased aldosterone production and reduced sodium ion and water loss in rats. The plasma creatinine, urea and urine albumin concentration were normalized after the administration of Ocimum G. extract in rats treated with CP. Ocimum G. also decreased the plasma concentrations of Interleukin-(IL)-6, C-reactive protein and activity of myeloperoxidase and malondialdehyde in CP treated rats. CONCLUSION: Ocimum G. prevented kidney injury and enhanced renal function via inhibiting inflammation and oxidant-induced CP toxicity. The efficacy of Ocimum G. is related to the presence of various phytochemicals in the plant.

Barium chloride dose-dependently induced heart and lung injury in Wistar rats.

Barium (Ba) is one of the environmental pollutant metals that incite deleterious effects on human health. The present study investigated the effects of exposure to different doses of barium chloride (BaCl2 ) on heart and lung of Wistar rats. Rats were exposed to BaCl2 at 150, 300, and 600 mg/L for seven consecutive days. Results indicated that exposure to Ba caused heart and lung damage evidenced by significant increase in plasma lactate dehydrogenase and creatine kinase activities, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels, while high-density lipoprotein-cholesterol level decreased when compared with control. Moreover, BaCl2 significantly decreased superoxide dismutase, catalase, and acetylcholinesterase activities as well as glutathione level in heart and lung of the treated rats. Furthermore, the dose-dependent increase in cardiac and lung lipid peroxidation, advanced oxidative protein product and nitric oxide levels were accompanied by marked increase in metallothionein in the BaCl2 -treated rats. Administration of BaCl2 altered hematological parameters and significantly increased concentrations of interleukin-6 in the treated rats. Histology analysis showed significant alteration in the heart and lung tissues of Ba-treated rats. In conclusion, BaCl2 -induced heart and lung damages via disruption of antioxidant defense systems, and activation of inflammatory mediators and alteration in hematological parameters in rats.

Polyphenol-rich extract of Ocimum gratissimum leaves ameliorates colitis via attenuating colonic mucosa injury and regulating pro-inflammatory cytokines production and oxidative stress.

Colitis is a chronic inflammation and ulcer on the inner lining of the large intestine. For many centuries Ocimum gratissimum (OG) leaves have been used in folk medicine in Nigeria to treat inflammatory bowel diseases, however, to date, the anti-colitis effects of OG have not been scientifically proven. In this study we investigated the effects of polyphenol rich extract of Ocimum gratissimum (PREOG) leaf on colonic mucosa injury in colitis, its mechanisms, initial administration time and dosage. Dextran sodium sulfate (DSS)-induced rat colitis models was used. PREOG administration was initiated at 3 and 7 d after the model was established at doses of 200, 400 and 800 mg/kg for 7 d. 5-aminosalicylic acid (5-ASA) was used as a reference drug. The disease activity index (DAI), vascular permeability, markers of oxidative stress, granulocyte infiltration, inflammation and histopathological alteration were evaluated. Obvious colonic inflammation and mucosa injuries were observed in DSS-induced colitis groups. PREOG administration promoted repair of colonic mucosa injuries, attenuated inflammation, and decreased DAI scores in rats with colitis. PREOG also decreased the plasma concentrations of Interleukin-(IL)-6 and tumor necrosis factor (TNF)-α, and concentrations of myeloperoxidase, nitric oxide, cyclooxygenase-2 and malondialdehyde in the colon, and increased the plasma concentrations of IL-4 and IL-10 as well as the concentration of superoxide dismutase, catalase and reduced glutathione in the colon. The efficacy of PREOG was dosage dependent. In conclusion, OG repairs colonic mucosa injury in experimental colitis through its ant-inflammatory and ant-oxidant. Its efficacy related to initial administration time and dose.