Ahmad Ashfaq
Department of Pharmacy Practice, College of Pharmacy, University of Hafr Al Batin, Hafr Al Batin 39524, Saudi Arabia.
Life (Basel). 2022 Nov 8;12(11):1819. doi: 10.3390/life12111819.
(Background and Objectives): Renal ischemia perfusion injury is one of the major issues in kidney transplant. The aim of the study was to investigate the hypothesis that prophylactic treatment-with a hydrogen sulphide donor to an acute renal failure case of hypertensive rats-can minimize the ischemia reperfusion injury of the kidney which is beneficial for kidney transplant. To check this hypothesis, the present study was designed to investigate the effect of chronic administration of a hydrogen sulphide (HS) donor and sodium hydrosulfide (NaHS) on nuclear factor kappa B (NF-kB) and inter cellular adhesion molecule-1 (ICAM-1) concentration in non-renal failure (NRF) and acute renal failure (ARF) rats in the ischemia-reperfusion injury (IRI) model of the kidney in both normotensive WKY and hypertensive rats (L-nitro arginine methyl ester (L-NAME-induced); (Materials and Methods): A total number of 48 Sprague-Dawley rats were recruited into eight groups each consisting of six animals. Each of these eight groups was used to measure systemic and renal parameters, HS, antioxidant parameters in plasma, plasma concentration of NF-kB and ICAM-1 and renal cortical blood pressure. ARF was induced by single intraperitoneal (i.p.) cisplatin injection (5 mg/kg). Hypertension was induced by oral administration of L-NAME in drinking water for four weeks at 40 mg/kg/day. NaHS was administered (i.p) at 56 µmol/kg for five weeks while dL-propargylglycine (PAG), a HS generation inhibitor, was administered as a single intra-peritoneal injection (50 mg/kg). An acute surgical experiment was performed for the induction of renal ischemia for 30 min by renal artery clamping followed by reperfusion for three hours; (Results): Chronic administration of NaHS attenuated the severity of ARF in both normotensive and hypertensive animals (L-NAME) along with lowering the blood pressure in hypertensive groups. NaHS improved the oxidative stress parameters such as total superoxide dismutase (T-SOD), glutathione (GSH) and reduced the malondialdehyde (MDA) concentration along with reduction of NF-kB and ICAM-1 following renal IRI; Conclusions: These findings demonstrate that HS not only reduced the severity of cisplatin induced ARF but also reduced the severity of renal IRI by upregulating antioxidants along with decreased concentrations of NF-kB and ICAM-1 in normotensive and L-NAME induced hypertensive rats.
(背景与目的):肾缺血灌注损伤是肾移植中的主要问题之一。本研究的目的是探讨以下假说:对高血压大鼠急性肾衰竭病例给予硫化氢供体进行预防性治疗,可将肾脏的缺血再灌注损伤降至最低,这对肾移植有益。为验证这一假说,本研究旨在探讨慢性给予硫化氢(HS)供体硫氢化钠(NaHS)对正常血压WKY大鼠和高血压大鼠(L-硝基精氨酸甲酯(L-NAME)诱导)肾脏缺血再灌注损伤(IRI)模型中非肾衰竭(NRF)和急性肾衰竭(ARF)大鼠核因子κB(NF-κB)和细胞间黏附分子-1(ICAM-1)浓度的影响。(材料与方法):总共48只Sprague-Dawley大鼠被分为8组,每组6只动物。这8组中的每组均用于测量全身和肾脏参数、血浆中的HS、抗氧化参数、NF-κB和ICAM-1的血浆浓度以及肾皮质血压。通过单次腹腔注射顺铂(5 mg/kg)诱导ARF。通过在饮用水中口服L-NAME,以40 mg/kg/天的剂量持续四周诱导高血压。NaHS以56 µmol/kg的剂量腹腔注射给药五周,而HS生成抑制剂炔丙基甘氨酸(PAG)作为单次腹腔注射(50 mg/kg)给药。进行急性外科手术实验,通过夹闭肾动脉诱导肾脏缺血30分钟,随后再灌注3小时。(结果):慢性给予NaHS可减轻正常血压和高血压动物(L-NAME)中ARF的严重程度,同时降低高血压组的血压。NaHS改善了氧化应激参数,如总超氧化物歧化酶(T-SOD)、谷胱甘肽(GSH),并降低了丙二醛(MDA)浓度,同时在肾脏IRI后降低了NF-κB和ICAM-1的浓度。(结论):这些发现表明,在正常血压和L-NAME诱导的高血压大鼠中,HS不仅降低了顺铂诱导的ARF的严重程度,还通过上调抗氧化剂以及降低NF-κB和ICAM-1的浓度降低了肾脏IRI的严重程度。
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