ABSTRACT
A prevalent clinical problem including sepsis, shock, necrotizing enterocolitis, and mesenteric thrombosis is intestinal ischemia/reperfusion (I/R) injury. Humanin (HN), a recently identified mitochondrial polypeptide, exhibits antioxidative and antiapoptotic properties. This work aimed to study the role of HN in a model of experimental intestinal I/R injury and its effect on associated dysmotility. A total of 36 male adult albino rats were allocated into 3 equal groups. Sham group: merely a laparotomy was done. I/R group: for 1 h, clamping of the superior mesenteric artery was done, and then reperfusion was allowed for 2 h later. HN-I/R group: rats underwent ischemia and reperfusion, and 30 min before the reperfusion, they received an intraperitoneal injection of 252 µg/kg of HN. Small intestinal motility was evaluated, and jejunal samples were got for biochemical and histological analysis. I/R group showed elevation of intestinal NO, MDA, TNF- α, and IL-6 and decline of GPx and SOD levels. Furthermore, histologically, there were destructed jejunal villi especially their tips and increased tissue expression of caspase-3 and i-NOS, in addition to reduced small intestinal motility. Compared to I/R group, HN-I/R group exhibited decrease intestinal levels of NO, MDA, TNF- α, and IL-6 and increase GPx and SOD. Moreover, there was noticeable improvement of the histopathologic features and decreased caspase-3 and iNOS immunoreactivity, beside enhanced small intestinal motility. HN alleviates inflammation, apoptosis, and intestinal dysmotility encouraged by I/R. Additionally, I/R-induced apoptosis and motility alterations depend partly on the production of nitric oxide.
Subject(s)
Interleukin-6 , Reperfusion Injury , Male , Apoptosis , Caspase 3/metabolism , Caspase 3/pharmacology , Interleukin-6/metabolism , Ischemia , Reperfusion Injury/metabolism , Superoxide Dismutase , Tumor Necrosis Factor-alpha/metabolism , Animals , RatsABSTRACT
Ivermectin (Ive) has exceedingly efficient against several microorganisms including viruses; therefore, it could help as a potential treatment of COVID-19. Because of increasing consumption of ivermectin and vitamin C (Vit.C) in hope to treat COVID-19, and because of ivermectin nephrotoxic effects have not been fully clarified especially in juvenile age, it was conducted to examine the histopathological and biochemical effects of ivermectin on adult and juvenile kidneys, and to assess the possible protective role of Vit.C against this potential toxicity. Rats were divided to 4 subgroups (Control subgroup, Vit.C subgroup, Ive subgroup, and Vit.C+Ive subgroup), 1 week after 4 doses of ivermectin (0.4 mg/kg Ive±1.25 mg/kg Vit.C), blood samples obtained for assessment of kidney function test, part of kidneys prepared for determination of matrix metalloproteinase-9 and antioxidant enzymes essay. Other parts prepared for histopathological and ultrastructural examination. Results showed that administration of ivermectin led to attenuation in kidney function and in activities of the antioxidant enzymes and increase in matrix metalloproteinase-9 activity. In addition, there were histological damages (shrunken glomeruli, widened urinary space, cytoplasmic vacuolation and pyknotic nuclei with epithelial exfoliation, extravasated blood, and mononuclear cell infiltration) and immunohistochemistry revealed increase in percentage of Bax proapoptotic protein expression. Also, ultrastructure examination showed alteration in cell architecture. All these changes were more obvious in juvenile group while co-administration of Vit.C led to significant protection more in adult group. In conclusion, Ivermectin should be used cautiously especially in juvenile age, and co-administration of Vit.C is highly recommended.
