Sustained feeding of a diet high in fat resulted in a decline in the liver's insulin-degrading enzyme levels in association with the induction of oxidative and endoplasmic reticulum stress in adult male rats: Evaluation of 4-phenylbutyric acid.

The current study explored the impact of high fat diet (HFD) on hepatic oxidative and endoplasmic reticulum (ER) stress and its insulin degrading enzyme (IDE) content with the injection of 4-phenyl butyric acid (4-PBA) in adult male rats. Following the weaning period, male offspring were distributed among six distinct groups. The corresponding diet was used for 20 weeks, subsequently 4-PBA was administered for three consecutive days. Plasma glucose and insulin levels, HOMA-ß (homeostasis model assessment of ß-cell), hepatic ER and oxidative stress biomarkers and IDE protein content were assessed. Long-term ingestion of HFD (31 % cow butter) induced oxidative and ER stress in the liver tissue. Accordingly, a rise in the malondialdehyde (MDA) content and catalase enzyme activity and a decrease in the glutathione (GSH) content were detected within the liver of the HFD and HFD + DMSO groups. Consumption of this diet elevated the liver expression of binding immunoglobulin protein (BIP) and C/enhancer-binding protein homologous protein (CHOP) levels while reduced its IDE content. The HOMA-ß decreased significantly. The injection of the 4-PBA moderated all the induced changes. Findings from this study indicated that prolonged HFD consumption led to a reduction in plasma insulin levels, likely attributed to pancreatic ß cell malfunction, as evidenced by a decline in the HOMA-ß index. Also, the HFD appears to have triggered oxidative and ER stress in the liver, along with a decrease in its IDE content.

The effect of magnesium sulfate on gene expression and serum level of inflammatory cytokines in coronary artery disease patients.

PURPOSE: To evaluate the effect of oral magnesium sulfate (MgSO4) on the gene expression and serum levels of inflammatory cytokines including TNF-α, IL-18, IL-1ß, IL-6, and IFN-γ in patients with moderate coronary artery disease (CAD). METHODS: 60 CAD patients were selected based on angiography findings and were randomly divided into two groups that received 300 mg/day MgSO4 (n = 30) or placebo (n = 30) for 3 months. Gene expression and serum levels of inflammatory cytokines were assessed. RESULTS: After 3 months of intervention, gene expression and serum levels of IL-18 and TNF-α in the MgSO4 group were significantly less than the placebo group (P < 0.05). However, no significant difference in gene expression and serum levels of IL-1ß, IL-6, and IFN-γ was observed between the two groups (P > 0.05). In addition, within group analysis demonstrate that Mg-treatment significantly decrease serum level of TNF-α and IL-18 as compared to pretreatment. CONCLUSION: The results of our study demonstrate that 3-month magnesium sulfate administration (300 mg/day) to CAD patients could significantly decrease serum concentration and gene expression levels of IL-18 and TNF-α. Our findings support the potential beneficial effect of magnesium supplementation on alleviating CAD complications through modulating inflammatory cytokines.

Magnesium Supplementation Affects the Expression of Sirtuin1, Tumor Protein P53 and Endothelial Nitric Oxide Synthase Genes in Patients with Atherosclerosis: A Double-Blind, Randomized, Placebo-Controlled Trial.

Magnesium seems to play a role in improving cardiovascular function, but its exact mechanism is unknown. In this study, we hypothesized that magnesium could modulate the expression of genes involved in atherosclerosis. The aim of the present investigation was to evaluate the effect of magnesium sulfate on the expression of sirtuin1 (SIRT1), tumor protein p53 (TP53), and endothelial nitric oxide synthase (eNOS) genes in patients with atherosclerosis. This study was a placebo-controlled double-blind randomized clinical trial on 56 patients with angiographically proven atherosclerosis. Participants were randomly divided into two groups receiving 300 mg/day magnesium sulfate (n = 29) and placebo (n = 27) for three months (following up every month). Fasting blood samples were taken before and after the intervention and total RNA was extracted and used to evaluate the expression level of SIRT1, TP53, and eNOS genes by Real-Time PCR. The expression of eNOS gene was significantly increased (P < 0.0001) and the expression of TP53 gene was decreased (P = 0.02) in the magnesium sulfate group compared to the placebo group. But SIRT1 gene expression was not significantly different between the two groups. Our findings demonstrate that magnesium sulfate supplementation may have a protective role against the progression of atherosclerosis through upregulation of eNOS and downregulation of TP53 gene. Trial registration: This present clinical trial has been registered in the Iranian Registry of Clinical Trials (IRCT) with the registration code of "IRCT20151028024756N3", https://www.irct.ir/trial/29097?revision=114102. Registered on 16 December 2019.

The influence of renal ischemia-reperfusion injury on remote organs: The histological brain changes in male and female rats.

INTRODUCTION: Brain tissue was adversely affected by renal ischemia-reperfusion injury (renal IRI) in several studies. Moreover, we are awareness that kidney diseases are gender dependent, but there is not enough evidence of the impact of gender on renal IRI-induced brain injury. Hence, this study was designed to investigate gender differences in renal IRI-induced brain tissue injury in adult rats. MATERIALS AND METHODS: Forty Wistar rats (four groups) include two main groups (20 male and 20 female). Each of them was divided into two subgroups including 1 and 2: male and female sham-operated groups and 3and 4: male and female ischemia (ISC) groups were exposed to renal ischemia for 45 min and then 24 h reperfusion (male and female ISC 24 h). Sham groups were exposed to surgery without ischemia process. After reperfusion time, blood samples were obtained for the renal function measurements. The kidney and brain were removed and were fixed in a 10% formalin solution for pathological assessment. The left kidney was used to measure malondialdehyde (MDA) and nitrite. RESULTS: Renal IRI increased significantly levels of creatinine, blood urea nitrogen, kidney weight, and damage score in both genders (P < 0.05). Furthermore, brain injuries were significantly higher following 24 h of reperfusion in male and female groups. Serum nitrite level and MDA concentration of female rats decreased significantly in ISC 24 h group (P < 0.05) but not in male rats. CONCLUSION: The brain tissue of both genders, male and female, is affected by renal IRI as a remote organ. Female sex hormones may indicate a protective role against IR by the nitric oxide pathway and antioxidant signaling.

Magnesium Sulfate Improves Some Risk Factors for Atherosclerosis in Patients Suffering from One or Two Coronary Artery Diseases: A Double-blind Clinical Trial Study.

PURPOSE: Given the beneficial effect of MgSO4 on the cardiovascular system, this study was designed to investigate the effect of MgSO4 administration on suppressing some atherosclerotic risk factors in moderate coronary artery disease patients with one or two atherosclerotic vessels. PATIENTS AND METHODS: In a randomized double-blind placebo-controlled clinical trial study, 64 patients with moderate coronary artery disease (55-69% stenosis) were selected according to angiography findings. Patients were divided into four groups including patients with one or two atherosclerotic vessels treated with MgSO4 (Mg-treated-VR1, Mg-treated-VR2, respectively), placebo treated patients with one or two atherosclerotic vessels (Control-VR1, Control-VR2, respectively). The patients received either placebo or MgSO4 supplement capsule containing 300 mg MgSO4 for six months on a daily basis. ESR, Ca/Mg ratio, urine Mg level, serum Mg, fibrinogen, homocysteine, uric acid, Na, K, Ca, CRP, T3, T4, TSH, BUN, and Cr concentrations were measured at baseline and every three months. RESULTS: Serum T3, Ca, K, homocysteine, CRP, and Mg concentrations were significantly improved in Mg-treated groups compared to placebo groups. CONCLUSION: The results of this study showed that despite the slight change in serum magnesium level, oral administration of MgSO4for six months could slightly reduce the serum levels of some inflammatory and vascular factors in moderate coronary artery disease patients.

Magnesium Sulfate Administration in Moderate Coronary Artery Disease Patients Improves Atherosclerotic Risk Factors: A Double-Blind Clinical Trial Study.

Magnesium (Mg) deficiency is known to promote vascular and cardiac dysfunctions such as atherosclerosis. This study investigated the effect of oral MgSO4 therapy to improve lipid profile and serum oxidized LDL level and its receptor (LOX1) in moderate coronary atherosclerotic patients. In this randomized double-blind placebo-controlled clinical trial study, 64 patients with moderate coronary artery disease were selected according to angiography findings. Participants were divided into 2 groups including Mg-treated (n = 32) and placebo (n = 32) The patients received either placebo or MgSO4 supplement capsule, containing 300 mg MgSO4 for 6 months on a daily basis. Lipid profile, HbA1c, 2h postprandial (2hpp) blood glucose, fasting blood sugar, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), oxidized low-density lipoprotein, and lectin-like ox-LDL receptor 1 (LOX1) concentrations were measured at baseline and every 3 months. HbA1c, serum LOX1, and oxidized low-density lipoprotein concentrations were significantly lower in the Mg-treated group than the placebo group 3 months after MgSO4 administration. 2hpp, serum low-density lipoprotein cholesterol, SGPT, SGOT levels, and HbA1c levels significantly improved in the Mg-treated group compared with the placebo-received group. Overall, the results of this study showed that magnesium treatment improved some of the major risk factors of atherosclerosis. According to the results of liver function tests (SGOT and SGPT), magnesium therapy seems to be safe in patients with moderate atherosclerotic plaque. Therefore, it is suggested that magnesium to be used along with other atherosclerosis control drugs.

Effect of the Administration of Solanum nigrum Fruit on Prevention of Diabetic Nephropathy in Streptozotocin-induced Diabetic Rats.

BACKGROUND: Our previous study showed antidiabetic effect of aqueous extract of Solanum nigrum Linn fruit (SNE). OBJECTIVE: This study was designed to explore the antidiabetic and nephroprotective effects of SNE in diabetic rats. MATERIALS AND METHODS: Animals were divided into nine groups to undergo two experiment protocols: Two groups served as nondiabetic controls (NDCs), while the other groups had diabetes induced with a single injection of streptozotocin. SNE-treated diabetic (D-SNE) and SNE-treated controls (NDC-SNE) received 1 g/L of SNE added to the drinking water and insulin-treated diabetic (D-I) for 8 weeks. Furthermore, there were four groups (D-SNE, NDC-SNE, D-I, D) in the second protocol to examine diabetic nephropathy (DN) for 16 weeks. Blood urea nitrogen (BUN), creatinine (Cr) magnesium, nitric oxide (NO), and malondialdehyde (MDA) levels were measured. Both kidneys were isolated to measure MDA, NO levels, and renal damage. RESULTS: SNE could decrease blood glucose level in diabetic rats. In addition, SNE was more effective than insulin in controlling blood glucose. SNE could decrease BUN, Cr levels, and kidney weight and damage after 8 and 16 weeks of administration. Plasma and kidney levels of NO and MDA also decreased. CONCLUSION: Our results support the hypothesis that SNE could play a role in the management of diabetes and the prevention of DN. SUMMARY: The aqueous extract of Solanum nigrum Linn fruit (SNE) (1 g/L via drinking water) was studied on streptozotocin-induced diabetic rats to prevent diabetic nephropathy (DN). The results suggest that SNE in addition to the management of diabetes could have a beneficial effect on the prevention of DN. Abbreviations Used: SNE: Extract of Solanum nigrum Linn fruit, NDCs: Nondiabetic controls, STZ: Streptozotocin, D-SNE: SNE-treated diabetic, NDC-SNE: SNE-treated controls, D-I: Insulin-treated diabetic, BUN: Blood urea nitrogen, Cr: Creatinine, Mg: Magnesium, NO: Nitric oxide, MDA: Malondialdehyde, DN: Diabetic nephropathy, BW: Body weight, FBG: Fed blood glucose, KW: Kidney weight, TBA: Thiobarbituric acid, IPGTT: Intraperitoneal glucose tolerance test, AUC: Aria under the curve, GFR: Glomerular filtration rate.

Cisplatin-Induced Nephrotoxicity; Protective Supplements and Gender Differences

Cisplatin (CDDP) has been widely used as a chemotherapeutic agent for solid tumors. The most common side effect of CDDP is nephrotoxicity, and many efforts have been made in the laboratory and the clinic to employ candidate adjuvants to CDDP to minimize this adverse influence. Many synthetic and herbal antioxidants as well as trace elements have been investigated for this purpose in recent years and a variety of positive and negative results have been yielded. However, no definitive supplement has so far been proposed to prevent CDDP-induced nephrotoxicity; however, this condition is gender related and the sex hormone estrogen may protect the kidney against CDDP damage. In this review, the results of research related to the effect of different synthetic and herbal antioxidants supplements are presented and discussed with suggestions included for future work.

N-acetylcysteine Prevents Kidney and Lung Disturbances in Renal Ischemia/Reperfusion Injury in Rat.

BACKGROUND: One of the most common causes of acute kidney injury (AKI) is kidney ischemia/reperfusion injury (IRI). The distant organ injury such as acute lung injury is one of the side effects of AKI or kidney IRI. In this study, we performed bilateral renal IRI in rats and the protective role of N-acetylcysteine (NAC) in kidney and lung was investigated. METHODS: Rats (n = 30) were randomly assigned to four experiment groups. The group 1 was assigned as sham-operated group. Before kidney IRI performance, the others groups were treated with saline (group 2), 150 mg/kg (group 3) or 500 mg/kg (group 4) of NAC, and the treatment were continued daily after IRI for next 3 days. At day 3, the all groups' animals were subjected for the measurements. RESULTS: The serum level of blood urea nitrogen (BUN) and creatinine (Cr) in the control group increased significantly (P < 0.05), and administration of NAC (150 mg/kg) decreased the serum levels of Cr and BUN. However, only the serum level of Cr decreased significantly (P < 0.05). NAC did not improve kidney weight and damage; however, its low dose (150 mg/kg) attenuated the lung injury score (P < 0.05) when compared with the control group. No significant differences were observed in lung water content and endothelial permeability, serum levels of malondialdehyde and nitrite between the groups. CONCLUSIONS: Low dose of NAC as a protectant agent may protect the kidney function and lung tissue damage after kidney IRI.

Protective role of recombinant human erythropoietin in kidney and lung injury following renal bilateral ischemia-reperfusion in rat model.

BACKGROUND: Acute kidney injury (AKI) has been recognized as one of the most complex clinical complications in modern medicine, and ischemia/reperfusion (I/R) injury is well-known as a main reason of AKI. In addition, AKI leads to important systemic consequences such as acute lung injury. This study was designed to investigate the role of erythropoietin (EPO) on kidney function makers and tissue damage; and lung endothelial permeability and lung water content (LWC) in bilateral renal I/R injury model in rats. METHODS: Male Wistar rats were randomly divided into three groups of sham, I/R, and I/R treated with EPO (I/R + EPO) groups. The I/R and I/R + EPO groups were subjected to bilateral renal I/R injury; however, only the I/R + EPO group received EPO (500 IU/kg, i.p.) 2 h before ischemia surgery, and the same dose was continued once a day for 3 days after ischemia. The sham group underwent a surgical procedure without ischemia process. RESULTS: The blood urea nitrogen (BUN) and serum creatinine (Cr) levels, kidney tissue damage score (KTDS), and kidney weight (KW) per 100 g body weight significantly increased in I/R group (P < 0.05). EPO administration decreased levels of BUN and Cr significantly (P < 0.05), and KTDS and KW insignificantly (P = 0.1). No significant differences in kidney and serum levels of malondialdehyde, and lung vascular permeability and LWC were observed between the groups. The serum and kidney levels of nitrite were not significantly different between I/R and sham groups; however, administration of EPO increased the renal level of nitrite (P < 0.05). CONCLUSIONS: EPO protected the kidney against I/R injury; however, it may not protect the lung tissue from the damage induced by renal I/R injury in rats.