Hepatotoxicity following separate administration of two phosphodiesterase-5 inhibitors (sildenafil & tadalafil) and opioid (tramadol); evaluation of possible reversal following their withdrawal.

The use of phosphodiesterase-5 inhibitors (PDE5i) and tramadol in the absence of erectile and ejaculatory dysfunctions in Nigeria has become a norm. In this study, we comparatively assess the effects of chronic use of these drugs on hepatotoxicity. Fifty male albino wistar rats weighing 180–200g were randomly assigned into 5 groups (n=10) as follows; control, sildenafil (1mg/100g b.w), tadalafil (1mg/100g b.w), tramadol (2mg/100g b.w) and sildenafil+tramadol treated group (1mg/100g and 2mg/100g b.w, respectively). Drugs were orally administered, once, every two days for 8weeks, at the end of which five animals were sacrificed per group (batch 1), while the remaining five animals per group were allowed for another 8weeks without drug administration (batch 2). Serum concentration of liver enzymes (AST, ALT and ALP) and bilirubin were assessed in both batches. Serum concentrations of AST, ALT, ALP, total bilirubin and unconjugated bilirubin were significantly (p<0.001) increased in all treated groups (batch 1), while conjugated bilirubin concentration was significantly (p<0.001) reduced in all treated groups, compared with control. Serum concentrations of AST and ALT were significantly reduced in sildenafil (p<0.01), tadalafil (p<0.05), tramadol (p<0.001) and sildenafil+tramadol (p<0.001) recovery groups, compared with their treated groups. Total and unconjugated bilirubin fractions were significantly (p<0.05 and p<0.01, respectively) reduced in tadalafil recovery group, compared with the treated group. Sildenafil+tramadol recovery group showed significantly (p<0.001) reduced total and unconjugated bilirubin concentrations, compared with the treated group. Chronic administration of PDE5i and tramadol reversibly altered liver functions.

Biochemical Effects of Some Traditional Nigerian Diets in Experimental Diabetic Rat Models.

Diet, besides its simplicity and affordability, has been clinically recommended as the first line of intervention in type 2 diabetes. However, compliance with the so-called diabetic diet has been notoriously poor, mostly because the social and cultural aspects of eating as well as the degree of difficulty involved in entrenching permanent changes in diet have greatly been underestimated. The present study therefore evaluated the suitability of some traditional Nigerian diets namely Garri with afang soup (GAS), pounded yam with edikang ikong soup (PYES) and ekpang nkukwo (EN) in alloxan diabetic rats. 15-day feeding with GAS and PYES respectively reduced (P<0.05) fasting blood glucose by 25.61% and 25.19%, compared to the reference diet, plantain with beans (37.22%). The glucose lowering effect of EN was however, not significant. Except GAS, the effect of the test diets on serum lipid profile was similar and comparable to the reference diet. Further, the impact on serum biochemical indices - β-carotene, total protein, albumin, urea and creatinine, though not dramatic, was not different from the reference diet, except serum β-carotene that was higher in the reference diet-fed animals than others (P<0.05). Taken together, these results suggest that the studied diets, can potentially offer the patients the needed dietary diversification in diabetes management.

Hypoglycaemic Effect and Proximate Composition of Some Selected Nigerian Traditional Diets Used in Management of Diabetes Mellitus.

Selected traditional Nigerian diets: Garri with afang soup, pounded yam with edikang ikong soup and ekpang nkukwo alongside a reference diet, plantain with beans porridge, were investigated for their efficacy for use in management of diabetes mellitus. The proximate composition of the diets was analysed using standard methods and thereafter fed to alloxanized rats for 15 days, while monitoring the changes in weight and blood glucose. Fasting blood glucose (FBG) results was significantly reduced (p<0.05) (initial and final) upon feeding garri with afang soup (25.61%) and pounded yam with edikang ekong soup (25.19%) relative to the diabetic control (5.19%). These reductions compared well with the reference diet, although its extent of glycaemic control was higher (37.22%). Body and relative liver weight changes over the period animals received the traditional diets were not significantly different (p>0.05) from that of the reference diet. Whereas the proximate composition components including crude proteins, fibre, ash and carbohydrate were not significantly different (p>0.05) compared to the reference diet; only crude fat and hence caloric value was significantly higher (p<0.05) in reference diet compared to the three traditional diets. From the results of this investigation, it is clear that the traditional diets studied can be effective in glycaemic control, hence could serve as effective substitutes for plantain with beans, usually recommended by health care givers.

Effect of Combined Leaf Extracts of Vernonia amygdalina (Bitter Leaf) and Gongronema latifolium (Utazi) on the Pancreatic β-Cells of Streptozotocin- Induced Diabetic Rats.

The study evaluated the effect of combined extracts of Vernonia amygdalina (VA) and Gongronema latifolium (GL) on the pancreas of streptozotocin (STZ) induced diabetic Wistar rats. Thirty-two (32) albino rats were divided equally into 4 groups. Groups A and B which served as normal (NC) and diabetic (DC) controls respectively, received placebo treatment. The diabetic test groups C and D were respectively treated with combined extracts of VA and GL (200mg/kg b. w., p. o.) and insulin, (humulin 5 IU/kg, s.c.) for 28 days. Thereafter, the animals were sacrificed and blood and pancreas were collected for serum glucose and histological evaluation, respectively. Changes in animal weight were also measured within the period. From the results it was revealed that both the combined extracts and humulin significantly increased the animals’ body weight (p<0.05) from -10.5% reduction in the DC, to 7.6% and 8.9% respectively. In the same order, serum glucose significantly decreased (p<0.05) by 12.49% and 14.96% after the 28-day treatment compared to DC. The extent of reversal of hyperglycemia in the extract treated animals compared well with the insulin treated group. The biochemical results were corroborated with results of histological evaluations: The pancreatic β-cells of DC animals which were distorted and degenerated with shrunken cell mass as against prominent islet cells with normal exocrine pancreas of NC animals became rapidly proliferated upon intervention with the combined extracts, suggesting a possible regeneration of the islet cells. On the otherhand, intervention with humulin did not produce observable differences in the cyto-architecture of the pancreatic islets compared to the diabetic control, confirming an extra-pancreatic mechanism of insulin.