Tag Archives: ischemia-reperfusion
Cardioprotective effect of Ginger in a rat model of myocardial damage and its possible intervention in PERK-ATF4-CHOP-PUMA apoptotic pathway
M. M. Mohammed1*, N. A. A. Osman2, F. M. Mourad3, M. F. Abedelbaky1
1Department of Biochemistry, Faculty of Medicine, Minia University, El-Minia, Egypt;
2Department of Pathology, Faculty of Medicine, Minia University, El-Minia, Egypt;
3BS Pharm, Faculty of Pharmacy, Deraya University, El-Minia, Egypt;
*e-mail: mostafa.mohamed@mu.edu.eg
Received: 11 March 2023; Revised: 27 March 2023;
Accepted: 13 April 2023; Available on-line: 27 April 2023
For today the exact mechanisms of myocardial infarction and ischemia/reperfusion injury are still not fully understood. ER stress and integrated stress response pathways are thought to play an essential role in myocardial damage. This includes activation of endoplasmic reticulum kinase (PERK), induction of activating transcription factor 4 (ATF4), expression of pro-apoptotic transcription factor (CHOP) and P53 up-regulated modulator of apoptosis (PUMA) involved in apoptosis control. We used a rat model of isoproterenol-induced myocardial damage to elucidate the possible cardioprotective effect of Ginger through the influence on ER stress-induced apoptotic pathway. We also compared its effect with Captopril, inhibitor of angiotensin-converting enzyme. Male albino Wistar rats received 1.0 or 2.0 ml of Zingiber officinale (Ginger) powder suspension (200 mg/ml) daily by intra-gastric intubation for 28 days. Isoproterenol at a dose of 85 mg/kg was IP injected on the 27th and 28th days. Serum aspartate transaminase (AST) level was measured using kinetic kit. Heart tissue was used for RNA extraction, evaluation of gene expression by Q-RT-PCR, immuno-histochemical determination of caspase-3 expression and histopathological studies. Our results showed that Isoproterenol administration increased CHOP-mRNA expression 4 folds in cardiac muscle tissue compared to normal control. Ginger pretreatment significantly decreased both CHOP and ATF4, and PUMA mRNA expression compared to Isoproterenol-treated groups. A significant reduction in ATF4 mRNA expression in a group pretreated with Captopril and Ginger compared to normal control group was observed. The results showed that Ginger reduced AST serum levels which correlated with results of histopathological studies of heart tissue. Our findings suggest that the protective effects of Ginger against myocardium damage induced by Isoproterenol may be mediated by reducing the endoplasmic reticulum stress by affecting the ATF4-CHOP-PUMA pathway.
Leptin and curcumin affect renal ischemia-reperfusion injury via modulation of P65 and Bax genes expression
M. M. Ragy1, M. M. Ramzy2*
1Physiology Department, Faculty of Medicine, Minia University, Misr-Aswan Road, Egypt;
2Biochemistry Department, Faculty of Medicine, Minia University, Misr-Aswan Road, Egypt;
*e-mail: maggiemaher24@gmail.com
Received: 01 June 2020; Accepted: 17 December 2020
Ischemia and reperfusion are natural steps during kidney transplantation, and ischemia-reperfusion injury is a critical condition in which physicians must preserve organ function and control cell damage. As leptin is thought to play an important role in the regulation of the immune system and inflammation and curcumin is a potent anti-fibrotic agent, both agents are promising to have therapeutic impact on renal damage. The present study was designed to evaluate the effects of leptin and curcumin on renal ischemia-reperfusion injury. Forty adult male albino rats were divided into four groups: control; ischemia-reperfusion (I/R), leptin-treated (leptin was injected intraperitoneally at a dose 100 μg/kg for 3 days prior to ischemia) and curcumin-treated (curcumin was given orally at a dose of 50 mg/kg/day for 5 days before ischemia). All rats were sacrificed 24 hours after reperfusion. Serum urea and creatinine, renal malondialdehyde and total antioxidant capacity were measured. Renal TNF-α was assayed by ELISA and P65 and Bax mRNA expression were determined using RT-PCR. Our results demonstrated a significant increase in P65 and Bax mRNA expression after renal ischemia-reperfusion injury compared to control group. Both leptin and curcumin prevented oxidative damage of the renal tissues as they lowered MDA and nitric oxide levels, increased antioxidant capacity and decreased TNF-α level. It was shown that protective leptin and curcumin effect against kidney IR-induced oxidative injury was associated with a down-regulation of P65 and Bax expression. These results show that ischemia-reperfusion leads to renal damage and also they reveal that both leptin and curcumin have protective implications which may be promising agents for avoiding various adverse effects.