Upregulation of Uric Acid Production and Caspase 3 Signalling Mediates Rohypnol-Induced Cardiorenal Damage.

The global prevalence of illicit drug use is on the increase with attendant complications like cardiorenal collapse. One such substance of abuse is rohypnol. Despite its ban in most countries, it remains a popular substance of abuse. Whether or not rohypnol induces cardiorenal injury and the associated mechanism is yet to be elucidated. Therefore, the present study investigated the effect of rohypnol on cardiorenal integrity and functions, and glucolipid metabolism. Forty-eight male Wistar rats randomized into six groups (n = 8/group) received (per os) vehicle, low-dose (2 mg/kg) and high-dose (4 mg/kg) rohypnol once daily for twenty eight days, with or without a cessation period. Data revealed that rohypnol exposure irreversibly caused insulin resistance, hyperglycaemia, and dyslipidaemia. This was accompanied by reduced cardiorenal mass and impaired cardiorenal cytoarchitecture and function. Furthermore, rohypnol treatment promoted oxidative stress, inflammation, genotoxicity, and decreased cardiorenal activities of Na+-K+-ATPase, Ca2+-ATPase, and Mg2+-ATPase. These alterations were associated with enhanced uric acid generation and caspase 3 activity in the cardiorenal complex. Thus, this study reveals that rohypnol exposure triggers cardiorenal toxicity with incident insulin resistance, glucolipid and cardiorenal proton pump dysregulation, altered redox state, and inflammation via enhancement of uric acid generation and caspase 3-dependent mechanism.

Effect of ethanolic extract of Cryptolepis sanguinolenta stem on in vivo and in vitro glucose absorption and transport: Mechanism of its antidiabetic activity.

OBJECTIVE: Extracts from various morphological parts of Cryptolepis sanguinolenta are widely used traditionally in folklore medicine in many parts of the world for the management, control, and/or treatment of a plethora of human ailments, including diabetes mellitus. In order to scientifically appraise some of the ethnomedical uses of Cryptolepis sanguinolenta, the present study was undertaken to investigate its influence at varying doses on intestinal glucose absorption and transport in relation to its hypoglycemic and hypolipidemic effects in rat experimental paradigms. MATERIALS AND METHODS: The animals used were divided into four groups. Control animals received 2 ml of distilled water, while treated groups received 50, 150, and 250 mg/kg bw of Cryptolepis sanguinolenta extract per oral respectively daily for 21 days. RESULTS: Cryptolepis sanguinolenta led to a significant decrease in glucose transport and absorption. It also caused significant reductions in plasma glucose, total cholesterol, triglyceride, and LDL cholesterol. Biochemical changes observed were suggestive of dose dependence. Histopathological studies also showed increased sizes of ß cells of the pancreas. CONCLUSION: The findings in these normoglycemic laboratory animals suggest that Cryptolepis sanguinolenta has hypoglycemic and hypolipidemic activities, possibly by reducing glucose absorption and transport, and enhancing the structural and functional abilities of the ß cells. This is the first study to report the effect of Cryptolepis sanguinolenta on intestinal glucose absorption. This effect could be attributed to its major bioactive principle, cryptolepine, an indoloquinoline alkaloid. This study thus lends credence to the use of Cryptolepis sanguinolenta in the management of diabetes mellitus.