Hemin Attenuates Cisplatin-Induced Acute Renal Injury in Male Rats

Alkahtani, Mohammed Ali; Abdel‐Moneim, Ashraf M.; Elmenshawy, Omar M.; Elkersh, Mohamed A.

doi:10.1155/2014/476430

Cited by 34 publications

(14 citation statements)

References 62 publications

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“…In addition, hemin inhibited the nuclear factor erythroid 2-related factor 2 (Nrf2) activating antioxidant response elements, which regulated genes for many antioxidant enzymes (Al-Kahtani et al 2014). Al-Kahtani et al (2014) have also reported that hemin-mediated increase of HO-1 activity was proved enough to decrease the NO-dependent pathological and infl ammatory conditions that support the obtained results in our study. Cross link exists between HO and NOS systems.…”

supporting

confidence: 88%

Eff ects of hemin, a heme oxygenase-1 inducer in L-arginine-induced acute pancreatitis and associated lung injury in adult male albino rats

Aziz

Kamel

Rifaai

2017

Endocrine Regulations

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Objective. Th e aim of the current study was to assess the protective outcome of hemin, a heme oxygenase-1 (HO-1) inducer on L-arginine-induced acute pancreatitis in rats. Acute pancreatitis (AP) is considered to be a critical infl ammatory disorder with a major impact on the patient health. Various theories have been recommended regarding the pathophysiology of AP and associated pulmonary complications.Methods. Twenty-four adult male albino rats were randomly divided into four groups: control group, acute pancreatitis (AP), hemin pre-treated AP group, and hemin post-treated AP group.Results. Administration of hemin before induction of AP signifi cantly attenuated the L-arginine-induced pancreatitis and associated pulmonary complications characterized by the increasing serum levels of amylase, lipase, tumor necrosis factor-α, nitric oxide, and histo-architectural changes in pancreas and lungs as compared to control group. Additionally, pre-treatment with hemin signifi cantly compensated the defi cits in total antioxidant capacities and lowered the elevated malondialdehyde levels observed with AP. On the other hand, post-hemin administration did not show any protection against L-arginine-induced AP.Conclusions. Th e current study indicates that the induction of HO-1 by hemin pre-treatment signifi cantly ameliorated the L-arginine-induced pancreatitis and associated pulmonary complications may be due to its anti-infl ammatory and antioxidant properties.

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supporting

confidence: 88%

Eff ects of hemin, a heme oxygenase-1 inducer in L-arginine-induced acute pancreatitis and associated lung injury in adult male albino rats

Aziz

Kamel

Rifaai

2017

Endocrine Regulations

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“…GENERATION OF SITE-SPECIFIC TRANSGENIC HO-1 MICE prone to developing AKI (11,23). Several studies have proposed oxidative stress as a major determinant of the pathophysiology during cisplatin injury, and in corroboration, induction of antioxidants, such as HO-1, or supplementation with N-acetyl cysteine before cisplatin administration has led to a favorable response (1,2,4,11,23). We chose to address the effects of HO-1 expression in cisplatin nephrotoxicity for two reasons.…”

Section: F389mentioning

confidence: 99%

Proximal tubule-targeted heme oxygenase-1 in cisplatin-induced acute kidney injury

Bolisetty

Traylor

Joseph

et al. 2016

American Journal of Physiology-Renal Physiology

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Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the breakdown of heme to biliverdin, carbon monoxide, and iron. The beneficial effects of HO-1 expression are not merely due to degradation of the pro-oxidant heme but are also credited to the by-products that have potent, protective effects, including antioxidant, anti-inflammatory, and prosurvival properties. This is well reflected in the preclinical animal models of injury in both renal and nonrenal settings. However, excessive accumulation of the by-products can be deleterious and lead to mitochondrial toxicity and oxidative stress. Therefore, use of the HO system in alleviating injury merits a targeted approach. Based on the higher susceptibility of the proximal tubule segment of the nephron to injury, we generated transgenic mice using cre-lox technology to enable manipulation of HO-1 (deletion or overexpression) in a cell-specific manner. We demonstrate the validity and feasibility of these mice by breeding them with proximal tubule-specific Cre transgenic mice. Similar to previous reports using chemical modulators and global transgenic mice, we demonstrate that whereas deletion of HO-1, specifically in the proximal tubules, aggravates structural and functional damage during cisplatin nephrotoxicity, selective overexpression of HO-1 in proximal tubules is protective. At the cellular level, cleaved caspase-3 expression, a marker of apoptosis, and p38 signaling were modulated by HO-1. Use of these transgenic mice will aid in the evaluation of the effects of cell-specific HO-1 expression in response to injury and assist in the generation of targeted approaches that will enhance recovery with reduced, unwarranted adverse effects.

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“…It has been shown that HO-1 induction ameliorates acute and chronic kidney injury such as ischemia-reperfusion (Chen et al 2015), cisplatin (Al-Kahtani et al 2014), and 5/6 nephrectomy (Desbuards et al 2009). On the other hand, the inhibition of this enzyme was found to aggravate renal damage (Ishikawa et al 2001;Takizawa et al 1998).…”

Section: R a F Tmentioning

confidence: 99%

Vascular function and arginine and dimethylarginines in gentamicin-induced renal failure: a possible effect of heme oxygenase 1 inducer hemin

Aycan-Ustyol

Kabasakal

Bekpınar

et al. 2017

Can. J. Physiol. Pharmacol.

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Increased oxidative stress and disturbance in nitric oxide bioavailability lead to endothelial dysfunction and cardiovascular complication in renal disease. Gentamicin (GM), a commonly used antibiotic exhibits a toxic effect on renal proximal tubules. Prevention of its nephrotoxicity is important. Therefore, we investigated whether heme oxygenase (HO)-1 induction influenced kidney and vascular function in GM-administered rats. GM (100 mg/kg/day; ip) was given to rats alone or together with hemin (20 mg/kg/alternate days; ip.) for 14 days. Plasma and kidney L-arginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) as well as kidney 4-hydroxynonenal (HNE) levels and myeloperoxidase (MPO) activity were measured. Histopathologic examinations of kidney and relaxation and contraction responses of aorta were also examined.GM increased serum SDMA, urea nitrogen (BUN), and creatinine levels and caused histopathologic alterations in kidney. GM elevated HO-1 protein and mRNA expressions, 4-HNE level, MPO activity and decreased antioxidant enzyme activities and L-arginine levels in kidney. Decreased relaxation and contraction were detected in the aorta. Hemin restored renal oxidative stress and inflammatory changes together with vascular dysfunction, but did not affect SDMA, BUN, and creatinine levels. It is concluded that HO-1 induction may be effective in improving renal oxidative stress, inflammation and vascular dysfunction mediated by GM.

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Hemin Attenuates Cisplatin-Induced Acute Renal Injury in Male Rats

Cited by 34 publications

References 62 publications

Eff ects of hemin, a heme oxygenase-1 inducer in L-arginine-induced acute pancreatitis and associated lung injury in adult male albino rats

Eff ects of hemin, a heme oxygenase-1 inducer in L-arginine-induced acute pancreatitis and associated lung injury in adult male albino rats

Proximal tubule-targeted heme oxygenase-1 in cisplatin-induced acute kidney injury

Vascular function and arginine and dimethylarginines in gentamicin-induced renal failure: a possible effect of heme oxygenase 1 inducer hemin

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