Abstract:Paracetamol (PCM) overdose can cause nephrotoxicity with oxidative stress as one of the possible mechanisms mediating the event. In this study, the effects of ethyl acetate extract of Zingiber zerumbet rhizome [200 mg per kg of body weight (mg/kg) and 400 mg/kg] on PCM-induced nephrotoxicity were examined. Rats were divided into five groups containing 10 rats each. The control group received distilled water while other groups were treated with extract alone (400 mg/kg), PCM alone (750 mg/kg), 750 mg/kg PCM+200 mg/kg extract (PCM+ 200-extract), and 750 mg/kg PCM+400 mg/kg extract (PCM+400-extract), respectively, for seven consecutive days. The Z. zerumbet extract was given intraperitoneally concurrent with oral administration of PCM. Treatment with Z. zerumbet extract at doses of 200 and 400 mg/kg prevented the PCM-induced nephrotoxicity and oxidative impairments of the kidney, as evidenced by a significantly reduced (P<0.05) level of plasma creatinine, plasma and renal malondialdehyde (MDA), plasma protein carbonyl, and renal advanced oxidation protein product (AOPP). Furthermore, both doses were also able to induce a significant increment (P<0.05) of plasma and renal levels of glutathione (GSH) and plasma superoxide dismutase (SOD) activity. The nephroprotective effects of Z. zerumbet extract were confirmed by a reduced intensity of renal cellular damage, as evidenced by histological findings. Moreover, Z. zerumbet extract administered at 400 mg/kg was found to show greater protective effects than that at 200 mg/kg. In conclusion, ethyl acetate extract of Z. zerumbet rhizome has a protective role against PCM-induced nephrotoxicity and the process is probably mediated through its antioxidant properties.

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Cardiovascular disease is the most common cause of death among diabetic patients worldwide. Hence, cardiovascular wellbeing in diabetic patients requires utmost importance in disease management. Recent studies have demonstrated that protein kinase C activation plays a vital role in the development of cardiovascular complications via its activation of mitogen-activated protein kinase (MAPK) cascades, also known as PKC-MAPK pathways. In fact, persistent hyperglycaemia in diabetic conditions contribute to preserved PKC activation mediated by excessive production of diacylglycerol (DAG) and oxidative stress. PKC-MAPK pathways are involved in several cellular responses, including enhancing oxidative stress and activating signalling pathways that lead to uncontrolled cardiac and vascular remodelling and their subsequent dysfunction. In this review, we discuss the recent discovery on the role of PKC-MAPK pathways, the mechanisms involved in the development and progression of diabetic cardiovascular complications, and their potential as therapeutic targets for cardiovascular management in diabetic patients.

Hyperglycemia-induced oxidative stress in diabetic conditions promotes alterations of function and other properties of the erythrocyte membrane. In this study, we examined the effects of palm vitamin E (200 mg/kg) on oxidative stress and the physical and morphological characteristics of erythrocyte membranes in streptozotocin-induced diabetic rats. Forty male rats were randomly divided into 4 groups as follows: Group 1, control group; Group 2, normal plus palm vitamin E treatment; Group 3, untreated diabetic group; and Group 4, diabetic plus palm vitamin E treatment. After 4 weeks of treatments, we determined complete blood count, erythrocyte osmotic fragility, erythrocyte morphology, levels of erythrocyte malondialdehyde and protein carbonyl, levels of erythrocyte glutathione and oxidized glutathione, and total plasma antioxidant capacity. The results of osmotic fragility were significantly higher in the diabetic group compared to the control and diabetic with palm vitamin E. There were significant morphological changes in the erythrocytes of the diabetic group compared to the control group. We also found a significant decrease in the hemoglobin concentration, hematocrit percentage, and erythrocyte distribution width in the diabetic group. Erythrocyte malondialdehyde and protein carbonyl levels were significantly higher in the diabetic group compared to the control group. Decreased levels of reduced glutathione and increased level of oxidized glutathione were observed in the diabetic group compared to the control and diabetic with palm vitamin E groups. Plasma total antioxidant capacity was significantly lower in the diabetic group than in the control group, whereas plasma total antioxidants in the diabetic with palm vitamin E group were significantly increased compared to the untreated diabetic group. In conclusion, 4 weeks of daily supplementation with 200 mg/kg palm vitamin E could reduce the levels of oxidative stress markers by inhibiting lipid peroxidation and protein oxidation in streptozotocin-induced diabetic rats.

Hematopoietic stem cells- (HSCs-) based therapy requires ex vivo expansion of HSCs prior to therapeutic use. However, ex vivo culture was reported to promote excessive production of reactive oxygen species (ROS), exposing HSCs to oxidative damage. Efforts to overcome this limitation include the use of antioxidants. In this study, the role of Hibiscus sabdariffa L. (Roselle) in maintenance of cultured murine bone marrow-derived HSCs was investigated. Aqueous extract of Roselle was added at varying concentrations (0–1000 ng/mL) for 24 hours to the freshly isolated murine bone marrow cells (BMCs) cultures. Effects of Roselle on cell viability, reactive oxygen species (ROS) production, glutathione (GSH) level, superoxide dismutase (SOD) activity, and DNA damage were investigated. Roselle enhanced the survival (P < 0.05) of BMCs at 500 and 1000 ng/mL, increased survival of Sca-1+ cells (HSCs) at 500 ng/mL, and maintained HSCs phenotype as shown from nonremarkable changes of surface marker antigen (Sca-1) expression in all experimental groups. Roselle increased (P < 0.05) the GSH level and SOD activity but the level of reactive oxygen species (ROS) was unaffected. Moreover, Roselle showed significant cellular genoprotective potency against H2O2-induced DNA damage. Conclusively, Roselle shows novel property as potential supplement and genoprotectant against oxidative damage to cultured HSCs.