Subacute and subchronic oral toxicity assessments of Acridocarpus smeathmannii (DC.) Guill. & Perr. root in Wistar rats.

Recent adverse herb reactions have stimulated interest documenting the safety profile of medicinal agents. Thus, subacute and subchronic oral toxicity of the hydroethanolic extract of Acridocarpus smeathmannii root (HEASR) in Wistar rats was investigated. In the 28 and 90-day subacute and subchronic toxicity tests, sixty-four rats (n = male: female = 1:1 = 32) were divided into four of eight/group and ninety-six (n = male: female = 1:1 = 48) into twelve/group respectively. Distilled water (10 mL/kg) or HEASR4, HEASR5 and HEASR6 (250, 500 and 1000 mg/kg/day) respectively were administered via oral gavage. Animals were killed humanely 24 h after the last administration. Using standard methods, acute oral toxicity dose of HEAR (2000 mg/kg) was non-lethal in rodents. Subacute administration of HEASR6 increased total bilirubin (p < 0.05) in female rats. HEASR moderately altered both haematological and biochemical indices in rats. HEASR6 administration reduced ovary weight in both studies while follicle stimulating hormone level in male was reduced at all doses used. HEASR modulated lipid peroxidation, sperm quality and elevated cyclooxygenase-2 levels in rats. Histology revealed gastritis and congestions in vital organs. The low-observed adverse effect level for HEASR was below 250 mg/kg for both sexes. Overall, HEASR demonstrated inherent toxicity evidenced by our current findings. The exaggeration of its folklore medicine applications calls for cautions.

Acridocarpus Smeathmannii (DC.) Guill. & Perr. Root enhanced reproductive behavior and sexual function in male wistar rats: Biochemical and pharmacological mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Novel therapeutic opportunities from medicinal agents continue to arouse scientific interest in recent times. Still, there is a dearth of information as regards experimental evidence generated from medicinal plants that would yield pharmacological agents for the treatment of erectile dysfunction. Acridocarpus Smeathmannii (DC.) Guill. & Perr. Root (ASR) has a long history as an aphrodisiac in African traditional medicine. Thus, this study investigated the reproductive potentials and associated biochemical mechanisms of its hydroethanolic extract (HEASR) in male Wistar rats. Also, the bioactive compounds were identified. MATERIALS AND METHODS: Fifty-four male albino rats (180 ±â€¯20 g) were divided into nine groups of six rats/group. Control, group 1 received normal saline (10 mL/kg). Groups 2-6 rats were administered sildenafil (1.43 mg/kg/day), mesterolone (0.36 mg/kg/day), doxazocin (0.03 mg/kg/day), HEASR1 (50 mg/kg/day) and HEASR2 (200 mg/kg/day) respectively. Others received co-administration of HEASR2 with standard drugs. Treatment lasted for 28 days via oral gavage. RESULTS: An acute oral toxicity of HEASR up to 2 g/kg produced no mortality in mice p.o. while the median lethal dose was estimated to be 810 mg/kg i.p. HEASR2 administration or in combination with sildenafil, mesterolone and doxazocin increased mounting frequencies on day 28 by 77.44%, 122.65%, 148.5% and 93.88% and sperm counts by 38.29%, 55.21%, 42.48%, and 48.98% respectively in treated rats. HEASR2 + sildenafil elevated testosterone and follicle stimulating hormone levels by 36.33% and 24.55% while HEASR2 + doxazocin elevated luteinizing hormone levels by 97.44% in rats. HEASR modulated prostate-specific antigen and malondialdehyde levels respectively. Reduced glutathione, superoxide dismutase, and catalase activities were raised in five selected organs. Serum nitric oxide but not cyclooxygenase-2 or tumor necrosis factor-α levels was moderately improved in rats. CONCLUSION: Overall, the results obtained demonstrated the potential of HEASR as a male reproductive enhancer, thus justify its folklore applications. Further, octadecanoic acid ethyl ester was the most abundant bioactive component present.

Toxicological evaluation of therapeutic and supra-therapeutic doses of Cellgevity® on reproductive function and biochemical indices in Wistar rats.

BACKGROUND: The misconception about dietary supplements being safe has led many into the in-patient wards. Cellgevity® (CGV) is a Max International premiere antioxidant supplement formula used by a large population. This study evaluated the effects of therapeutic and supra-therapeutic doses of CGV on reproductive function and biochemical indices in Wistar rats. METHODS: Seventy-two Wistar rats weighing 130 ± 15.8 g were grouped into two categories (male or female) of six rats per group. Control group received distilled water (10 ml/kg). Others received therapeutic (14.3 mg/kg or 28.6 mg/kg) and supra-therapeutic CGV doses (1000, 2000 or 3000 mg/kg) body weight per oral respectively. RESULTS: After 60 days, supra-therapeutic doses of CGV reduced sperm motility (p < 0.05) by 31.8%, 31.3% and 34.5% respectively and increased (p < 0.05) abnormality in sperms by 200%, 241% and 141.3% respectively. CGV altered male (luteinizing, follicle stimulating hormones and testosterone) and female reproductive hormones (luteinizing, follicle stimulating hormones estrogen and progesterone) respectively. Therapeutic doses of CGV elevated reduced glutathione, superoxide dismutase, catalase and glutathione S-transferase, although, this was exceeded by supra-therapeutic doses and more in females than male rats. Supra-therapeutic dose (3000 mg/kg CGV) decreased body weight in both male and female rats by 50% (F(1.5, 30) = 1.2, p = 0.041) and 62.7% (F(2.1, 30) = 0.38, p = 0.038) respectively in treated rats. Supratherapeutic (3000 mg/kg) dose of CGV increased (p < 0.05) creatinine level by 99.1% while serum total protein was reduced (p < 0.05) by 60.1% (2000 mg/kg) and 57.2% (3000 mg/kg) respectively in male animals. In Female rats, supra-therapeutic doses of CGV elevated creatinine levels by 72.2% (1000 mg/kg), 60.2% (2000 mg/kg) and 124.8% (3000 mg/kg) respectively and 3000 mg/kg produces elevated serum low density lipoprotein by 34.6% in treated rats. Serum cholesterol, triglycerides, albumin, alkaline phosphatase were unaltered by CGV dosing. Histology shows seminiferous tubules with reduced spermatogenic cells. Also, female rat kidney revealed acute tubular necrosis at highest dose used in this study. CONCLUSION: Overall, these data suggest that pro-oxidant potential of the supra-therapeutic CGV doses is evident. Hence, it is necessary that its administration be done with caution using appropriate doses.

Five traditional Nigerian Polyherbal remedies protect against high fructose fed, Streptozotocin-induced type 2 diabetes in male Wistar rats.

BACKGROUND: This present study sought to assess the modulatory effects of five Nigerian traditional polyherbal in high fructose-fed, streptozotocin-induced (HF-STZ) Type 2 diabetes (T2D) in rats. T2D was achieved via fructose feeding (20%W/V) ad libitum for 2 weeks and streptozotocin (STZ, 40 mg/kg) (15th Day) intraperitoneally. METHODS: Seventy-two hours after STZ injection, fourty-eight diabetic rats were divided into eight of 6 rats/group: Diabetic normal untreated, glibenclamide (GBLI, 0.07 mL/kg) or yoyo (YB, 0.43), ruzu (RB, 0.08), fajik (FJB, 0.20), oroki (OB, 0.16), and fidson (FB, 0.43)/ mL/kg bitters respectively. Controls normal and diabetic untreated groups received intragastric carboxylmethylcellulose (CMC, 1 mL/kg) for eleven days. RESULTS: T2D was characterized in rats by an increased (p < 0.001-0.05) blood glucose levels (BGL), total cholesterol, triglycerides, low-density lipoprotein and alanine aminotransferase compared with control CMC group. Similarly, hepatic and pancreatic malondialdehyde (MDA) were increased by 180 and 97% respectively. Polyherbal treatments demonstrated efficacies on BGL as follow: YB (55.6%, 160.7 mg/dL); RB (59.7%, 145.2 mg/dL); FJB (59.8%, 243.4 mg/dL); OB (60.8%, 194.5 mg/dL) and FB (61.3%, 203.3 mg/dL) respectively by day 11 (versus GBLI, 65.1%) compared with control untreated diabetic rats. Also, elevated TC, LDL cholesterol, ALT were lowered (p < 0.05) by YB, FJB, and FB respectively in rats. YB, FJB, and OB lowered MDA levels in treated rats. Further, YB, RB, FJB and FB restored changes in liver, and pancreas histopathology. Predominant non-polar bioactive include oleic, hexadecanoic, octadecanoic among others following gas chromatography-mass spectrophotometry analyses. CONCLUSION: Overall, these present results demonstrate anti-hyperglycemic potentials, although with cautions, of some polyherbal in T2D rats, which may, in part, be antioxidants mediated.

Celecoxib, a cyclooxygenase-2 inhibitor, offers chemoprevention against reproductive and neurobehavioural abnormalities induced by atrazine in male Wistar rats.

The cyclooxygenase-2/prostanoid pathway (COX-2) serves as a potential therapeutic target in various pathological conditions. Thus, the modulatory effect of celecoxib (CXB), a COX-2 inhibitor, in atrazine-induced toxicity was investigated. Five groups (n = 6 rats per group) of adult male Wistar rats received corn oil (2 ml/kg), atrazine (ATZ, 300 mg/kg) and CXB (5.7 mg/kg) respectively and their combinations via the oral route. Results obtained showed reduced (p < 0.05) sperm motility (25.8%) and counts (27.6%), testosterone (29.9%), luteinizing (33%) and follicle stimulating hormones (78.7%) plus elevated total cholesterol (112.3%), triglyceride (115.7%), malondialdehyde levels respectively in ATZ-treated rats. Similarly, ATZ administration causes reduced locomotion (33.6%), spontaneous motor activity (46.6%) and catalepsy effects (157.3%) respectively. However, CXB divided doses moderately reverse reproductive abnormalities, modulate neurobehavioural deficits and slightly preserved COX-2 elevation following ATZ intoxication. Furthermore, histopathology of testis shows improvement in treated rats. Overall, our data suggest chemopreventive actions via pharmacological inhibition of COX-2 activity during ATZ toxicity.

Safety evaluation of Bon-santé cleanser® polyherbal in male Wistar rats: Further investigations on androgenic and toxicological profile.

BACKGROUND: The global increase in acceptance and use of herbal remedies in recent times is still accompanied with poor knowledge of their potential adverse effects and the toxicological implications of their use are underestimated. METHODS: Bon-santé Cleanser® (BSC), a polyherbal containing Anogeissus leiocarpus, Terminalia ivorensis, Massularia acuminate and Macuna pruriens, is an "energizer and hormone booster". We assessed the effect of BSC on reproductive function after administration for 60 days in male Wistar rats. Rats (150-300 g) were assigned into four groups of 8/group. Control received distilled water (10 ml/kg) while other groups received BSC 250, 500 and 1000 mg/kg/day p.o. respectively. Animals were euthanized by cervical dislocation and samples collected for analysis. RESULTS: BSC (250 mg/kg) elevated (p < 0.05) follicle stimulating hormone and luteinizing hormone levels respectively. BSC decreased sperm motility and the live-dead ratio at 1000 mg/kg and reduced reproductive hormone at 500 mg/kg and 1000 mg/kg respectively. BSC at 500 mg/kg increased (p < 0.05, F = 3.18-13.21) testicular reduced glutathione level (50.3%) and catalase (43.7%) but not activities of superoxide dismutase, glutathione S-transferase, and malondialdehyde level. Further, BSC influenced Mg, Zn, Cu, P, Mn, Ni and Fe levels (p < 0.05). BSC (1000 mg/kg) decreased testis weight (p < 0.05) and induced mild inflammation characterized by atrophic tubules. CONCLUSION: Overall, our data suggest BSC at low doses may increase reproductive hormones regulated by FSH and LH as observed in this study. However, BSC administration should be done with caution as it may induce reproductive toxicity in large doses.

Safety evaluation of Bon-santé cleanser® polyherbal in male Wistar rats.

BACKGROUND: The potential harm of medicinal herbs has been recently observed following herbal toxicity studies after ingestion of polyherbal remedies. This was the rationale for the food and drug regulatory agency decision for thorough safety evaluation of herbal medicines. Androgenic, antipyretic, analgesic and anti-inflammatory potentials as well as chemical compositions of extracts of massularia acuminata, terminalia ivorensis, anogeissus leiocarpus and macuna pruriens respectively have been documented. Thus, Bon-santé cleanser® (BSC) is formulated from these medicinal plants with the intention to boost body hormones and energizes the body. Considering the wide usage of BSC, we investigated on its safety in male Wistar rats. METHODS: Thirty-two male Wistar rats weighing 201.9 ± 7.5 g were grouped into four treatment groups of eight per group. Group I, (control) received distilled water (10 ml/kg). Groups II-IV received 250 mg/kg, 500 mg/kg and 1000 mg/kg of BSC per oral respectively. Each group was treated for sixty days. RESULTS: Acute toxicity test, in male Wistar albino mice, showed that LD50 was 600 mg/kg via i.p. while 4 g/kg was nonlethal after oral administration in mice. Hepatic and renal biomarker enzymes were unaltered in all rats. Increased in PCV (p <0.05) was observed at 500 mg/kg. BSC modulates antioxidants biomarkers following sub-chronic administration and increased serum Na(+) (p >0.05). BSC at 1000 mg/kg caused mild inflammation of the liver and heart but not kidneys histologically. CONCLUSIONS: BSC has been found to be relatively safe in Wistar rats. Although, our findings indicate that herbal therapy with BSC should be done with caution as a mild alteration in the liver and heart architectures were observed.

The combined fixed-dose antituberculous drugs alter some reproductive functions with oxidative stress involvement in wistar rats.

The reproductive toxicity of combined fixed-dose first-line antituberculosis (CFDAT) regimen was assessed in rats. Thirty-two (32) Wistar rats weighing 168.1 ± 8.0 g were divided into four groups of eight rats per group. Two groups of male and female rats were administered oral distilled water (1.6 ml) and CFDAT drugs containing rifampicin, isoniazid, pyrazinamide and ethambutol (RIPE, 92.5 mg/m2 per body surface area) respectively for forty-five days. Serum follicle stimulating hormone, luteinizing and testosterone were reduced significantly (p < 0.05) in the treated male rats. Similarly, sperm count levels were decreased by 27.3% when compared with control. RIPE elevated serum oestrogen (p < 0.05), progesterone (p < 0.05) as well as prolactin (p > 0.05) levels in the treated females. In addition, RIPE reduced (p < 0.05) total proteins levels and increased (p < 0.05, 53%) catalase levels in male but not female animals. Superoxide dismutase, glutathione-S-transferase, glutathione peroxidase, reduced glutathione levels as well as lipid peroxidation were unaltered in all rats respectively. Histopathological studies revealed congested peritesticular vessels and no changes in the ovary when compared with control. Overall, our results demonstrate reproductive toxicity potentials of RIPE in the rat, thus, suggesting that these reproductive parameters be monitored during antituberculous chemotherapy.