Asian Pacific Journal of Tropical Biomedicine

333-342

Authors: Qi Li, Bo Wang, Kai-Wen Lin, Tang Deng, Qi-Feng Huang, Shuang-Qin Xu, Hang-Fei Wang, Xin- Xin Wu, Nan Li, Yang Yi, Ji-Chao Peng, Yue Huang, Jin Qian, Xiao-Ran Liu

Objective: To explore the protective effects of anthrahydroquinone- 2,6-disulfonate (AH2QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH2QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH2QDS group was given AH2QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL- 6, TNF-α, apelin-APJ (the apelin-angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH2QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH2QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH2QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH2QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH2QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH2QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH2QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH2QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH2QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH2QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.

351-356

Authors: Masud Eneji Sadiq, Chibuzo Egwuenu, Rabiu Saidu Umar Wasagu, Usman Zayyanu Umar, Bello Usman

Objective: To investigate the role of Mirabilis jalapa root extracts in restoration of glucose homeostasis in alloxan-induced hyperglycemic Wistar albino rats. Methods: Experimental hyperglycemic rats were treated daily with 200 and 400 mg/kg of Mirabilis jalapa extracts after initial fasting for 6 h. Two-hour postprandial glucose and changes in body weight were monitored during treatment. After 14 d, the rats were sacrificed and blood was collected for biochemical assessment of serum glucose and insulin levels, lipid profile, and oxidative stress markers. Histopathological examinations of harvested pancreas were also carried out. Results: Mirabilis jalapa root extracts at 200 and 400 mg/kg increased the body weight of hyperglycemic rats. Postprandial glucose levels of the extract-treated hyperglycemic groups progressively declined during treatment compared with the untreated hyperglycemic control group (P<0.05). The lipid profile indices of the untreated negative control group were significantly elevated (P<0.05), which were reversed by treatment with Mirabilis jalapa extracts. The remarkable increases in antioxidant enzyme activities and a significant decrease in malondialdehyde levels were observed in the hyperglycemic group treated with Mirabilis jalapa extracts. Mirabilis jalapa extracts also significantly increased serum insulin levels (P<0.05). In addition, histopathological examinations of the pancreas revealed a significant cell population within the islet nests of the extract-treated hyperglycemic groups. Conclusions: Mirabilis jalapa extract can restore glucose homeostasis and show hypoglycemic and hypolipidemic effects in hyperglycemic rats. Further studies are needed to verify the active components of the plant and the underlying mechanism of action in the future.