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Background and Aim: Deferasirox (Exjade) is an iron-chelating drug used in patients with beta-thalassemia major. Oxidative stress is among f the major causes of nephrotoxicity and its progression. Deferasirox, due to oxidative stress and increased cell apoptosis causes the dysfunction of renal tubules and renal toxicity. According to its antioxidant and anti-inflammatory properties, the present study explored the effect of vitamin C on deferasirox-induced kidney damage. Methods & Materials: This study was performed on 30 Wistar rats in 3 groups of control, deferasirox, and deferasirox plus vitamin C. To induce the nephrotoxicity, the intra-peritoneum injection of deferasirox (75 mg/kg/day) was used. After taking plasma from the blood samples of the explored rats, we determined the values of Cr, Na+, K+, Mg+, osmolality, and BUN in the obtained plasma and urine samples. The creatinine clearance, as well as the relative and absolute excretion of sodium and potassium, were also calculated. After separating the two kidneys, they were used for the histologic study with Hematoxylin and Eosin (H&E) staining, as well as Malondialdehyde (MDA) and Ferric Reducing Antioxidant Power (FRAP) biochemical studies. Ethical Considerations This study was approved by the Research Ethics Committee of Arak University of Medical Sciences (Code: IR.ARAKMU.REC.1396.309). Results: Cotreatment with deferasirox and vitamin C reduced renal tissue MDA and relative and absolute Na and K excretion and urine osmolarity; this method also increased creatinine clearance and renal tissue FRAP. Conclusion: The co-administration of vitamin C presented a significant protective effect on the renal toxicity induced by deferasirox. The protective property of deferasirox is because of the antioxidant impacts of vitamin C in reducing oxidative stress and lipid peroxidation.

Recent studies have shown that mesenchymal stem cells (MSCs) and their conditioned medium (CM) have potential therapeutic effects in animal models of neuropathic pain (NP). However, the mechanisms underlying these effects are not fully understood. Because of the leading involvement of purinergic receptors in the pathogenesis of NP, this study aimed to investigate the effect of MSCs-CM on the expression levels of P2X4 and P2X7 receptors in a rat model of NP induced by chronic constriction injury (CCI) of the sciatic nerve. CM was prepared from the rats’ bone marrow–derived MSCs culture. After that, NP rats were treated by intraperitoneal injection of CM, or Dulbecco’s modified Eagle’s medium (DMEM) 1 day before and 7 and 11 days after CCI surgery. The NP status was assessed in the treated animals using behavioral tests, including mechanical allodynia and thermal hyperalgesia, on days − 1, 3, 6, 9, 12, and 15 of the study. At the end of the study (Day 15), the animals were sacrificed, and the relative gene expression of P2X4 and P2X7 receptors were measured in the spinal cord using quantitative real-time PCR. The results demonstrated that in the CM-treated NP rats, mechanical allodynia and thermal hyperalgesia were significantly reduced compared with the DMEM-treated group. In addition, the expression levels of P2X4 and P2X7 receptors were noticeably prevented in the CM-treated group than the control group. These findings indicate that the antinociceptive effects of CM in the NP rats are partly mediated through preventing the upregulation of P2X4 and P2X7 receptors in the spinal cord.

Objective: Renal toxicity and ototoxicity are considered as the main side effects of aminoglycoside antibiotics, such as gentamicin. The present study aimed to investigate the effect of co-treatment by origanum vulgare extract on the gentamicin-induced renal toxicity. Methods: Adult male Wistar rats in the weight range of 200 to 250 grams were randomly assigned into four groups (n = 8): control, renal toxicity (with the intraperitoneal injection of gentamicin [100 mg/kg/day], for eight days), co-treatment with OV extract and gentamicin vehicle (with the intraperitoneal injection of normal saline and OV extract gavage [40 mg/kg], for eight days), co-treatment with OV ethanolic extract (with the intraperitoneal injection of gentamicin [100 mg/kg/day] and OV extract gavage [40 mg/kg]), for eight days. The amount of urea, creatinine, sodium, potassium, and osmolality were measured in the plasma and urine samples. The left kidney was used for the histological study and the right kidney was used to measure MDA and FRAP. Results: treatment with OV ethanolic extract significantly decreased the blood concentrations of creatinine, urea, the absolute excretion of sodium, the fractional excretion of sodium and potassium, and MDA, compared with the renal toxicity group. Besides, co-treatment with ethanolic extract of origanum Vulgare significantly increased creatinine clearance, urinary osmolality, and FRAP, compared with the renal toxicity group. Conclusion: The oral co-treatment with ethanolic extract of origanum vulgare has a protective effect on gentamicin-induced renal toxicity. This effect can be induced by reducing the oxidative stress caused by free radicals and reducing the amount of lipid peroxidation caused by gentamicin.

Background Ischemia-reperfusion (I-R) leads to acute kidney injury (AKI). The present study investigated the effects of nitroglycerine (NG) on improving renal dysfunctions caused by I-R in rats. Methodology Twenty-four rats were equally divided into four groups: (1) the control group, (2) the sham group, (3) the I-R group, and (4) NG-treated groups.NG (50 μg/kg) was injected intraperitoneally after induction of IR. I-R was induced through clamping of the bilateral renal artery and vein of both kidneys for 20 min followed by 24 h of reperfusion. Results NG significantly increased the creatinine clearance levels and renal blood flow rate (which was reduced by I-R). NG also significantly improved serum electrolytes (sodium and potassium) that were disordered by I-R. In addition, NG significantly offset impaired antioxidant defense mechanism and inhibited lipid peroxidation. Conclusions The results show NG has a protective effect on renal tissue against AKI caused by I-R. These protective effects mediated through antioxidant activity and decrease of lipid peroxidation.

Background Nephrotoxicity is the major side effects of aminoglycoside antibiotics such as gentamicin. The aim of this study was to investigate the therapeutic effects of Z.multiflora (ZM) hydroalcoholic extract on gentamicin-induced nephrotoxicity. Methods Twenty-eight male Wistar rats categorized into four groups: 1) the control group without injection, 2) the gentamicin treated group (100 mg/kg, i.p) 3) the gentamicin and Z. Multiflora treated group; Z. Multiflora extract(0.8 mg/ml in the drinking water) administered after gentamicin (100 mg/kg, i.p) 4) the normal saline and Z. Multiflora treated group; Z. Multiflora extract (0.8 mg/ml in the drinking water) administered after normal saline injection (2 ml/kg,i.p ). Results Post-treatment with ZM extract caused a significant reduction in the levels of plasma creatinine and blood urea nitrogen (BUN), absolute and fractional excretion of sodium, malondialdehyed (MDA) level in comparison to gentamicin group. In addition, ZM extract significantly increased creatinine clearance, urine osmolarity, and Renal blood flow (RBF) and the Ferric reducing ability of plasma (FRAP) level which had decreased compared to the control group as a result of treatment with gentamicin. Conclusion The above result indicated that ZM extract improved renal toxicity of gentamicin via reducing oxidative stress, oxygen-free radicals, and lipid peroxidation.

Background: Acute renal failure induced by ischemia / reperfusion (I/R) causes excretory functional disorders of nephrons. The purpose of this study is to evaluate the intake of oral rosemary extract (gavage) on hemodynamic changes and tissue damages caused by I/R. Materials and Methods: This study was conducted on 40 Sprague-Dawley male rats, composed of 4 groups (n=10) including control, sham, I/R+normal saline (I/R+NS) post-treatment and I/R+rosemary (I/R+RO) post-treatment. They were fed with 10 ml/kg of 8% aqueous extract or vehicle as gavages during the first 48 hours after I/R. To induce I/R, both renal artery and vein were blocked for 30 minutes followed by a reperfusion within 48 hours. Then urine and plasma samples were collected and histological study was also conducted after removal of both kidneys. Data were analyzed by SPSS-11.5 software. The one-way analysis of variance (ANOVA) and Duncan test were used for intergroup comparison and p≤ 0.05 was used as the significant level. The Kruskal–Wallis multiple comparison test was also used for doing histological analysisResults: Comparison of renal function between two groups of (I/R+RO) and (I/R+NS), showed a significant reduction in plasma creatinine (p=0.05), the blood urea nitrogen (p=0.05), absolute excretion of sodium (p=0.001) and an increase in absolute potassium excretion (p=0.01). Results of the histological study also indicated a significant decrease in the vascular congestion, Bowman’s capsule space and oxidative stress in the group (I/R+RO) in comparison with (I/R+NS).Conclusion: Treatment with rosemary may be effective in the reduction of the functional and histological effects of I/R.

Non-technical summary Due to the conservation of developmental pathways and genetic material over the course of evolution, non-mammalian ‘model organisms’ such as the zebrafish embryo are emerging as valuable tools to explore causes and potential treatments for human diseases. Ion channels are proteins that form pores and help to establish and control electrical gradients by allowing the flow of ions across biological membranes. A diverse range of key physiological mechanisms in every organ in the body depends on the activity of ion channels. In this paper, we show that a potassium-selective channel that underlies salt reabsorption and potassium excretion in the human kidney is also expressed in zebrafish in cells that are important regulators of salt balance. Disruption of the channel's expression in zebrafish leads to effects on the activity of the heart, consistent with a role for this channel in the control of potassium balance in the embryo.

Reperfusion injury leads to damage to the hemodynamic and functional parameters of the kidney. This study investigated the effects of oral administration of the aqueous extract of rosemary on improvement of changes induced by ischemia-reperfusion in rats.Fourty male Sprague-Dawley rats were divided into 4 groups. One group was the control, rates in another group underwent sham operation, and 2 groups were exposed to reperfusion injury. Rats in one of the reperfusion groups was treated with 8% oral aqueous extract of rosemary (10 mL/kg/d) for 1 week (rosemary group), and the other received normal saline for the same period of time (reperfusion group). Reperfusion injury was induced by bilateral occlusion of the renal artery and vein for 30 minutes and reperfusion for 24 hours. Examination of oxidative stress was done, including measurement of malondialdehyde and ferric reducing antioxidant power in urine and blood samples. Histological studies were performed on excised kidneys.The comparison between the rosemary and reperfusion groups indicated significant reductions in the levels of plasma creatinine, blood urea nitrogen, and absolute urinary excretion of sodium in the rosemary group. Similarly, the rosemary group presented a significant decrease in malondialdehyde and a significant increase in ferric-reducing antioxidant power. Histopathological examinations showed significant reductions in vascular congestion and cells exfoliation in the rosemary group, in comparison with the reperfusion group.Oral administration of the aqueous extract of rosemary prior to ischemia-reperfusion is effective in reducing functional and histopathological complications associated with acute kidney failure.