Stress In Kidney Tissues Research Articles

An Oxidative Stress Study on Curcumin and NanoCurcumin against Aluminum Phosphide-induced Kidney Injury in Rats: The Role of SIRT1/FOXO3 Signaling Pathway in Nephrotoxicity.

In this study, we have investigated the aluminium phosphide (ALP) toxicity on Renal Function and oxidative stress in kidney tissue of male rats and the possible protective role of Curcumin and nanoCurcumin against ALP-induced nephrotoxicity. Thirty-six adult male rats were divided into 6 groups (n=6). ALP (2 mg/kg oral administration) and control groups received Curcumin and nanoCurcumin (oral administration 100 mg/kg) or without it. After seven days of treatment, kidney parameters, oxidative stress biomarkers, and expression level of sirtuins1 (SIRT1)/Forkhead box protein O1 (FoxO1) pathway genes were evaluated in kidney tissue. In addition, histopathological changes in the kidney tissues were assayed. In the ALP group, compared to the control group, lipid peroxidation levels, urea, and creatinine were increased, and total antioxidant capacity and thiol groups decreased significantly p < 0.05. In Curcumin and nanoCurcumin groups compared to the ALP group, lipid peroxidation and creatinine decreased significantly p < 0.05. Also, Curcumin and nanoCurcumin improved the tissue damage caused by ALP. NanoCurcumin modulated the effect of ALP on the gene expression levels in SIRT1/FoxO1. The present study showed that ALP intoxication in kidney tissue can induce oxidative damage. Moreover, Curcumin and nanocurcumin, as potential antioxidants, can be effective therapeutics in ALP-induced nephrotoxicity.

Morphometric and functional changes in the kidney of rats induced by inorganic selenium.

Selenium (Se) is an essential trace element. Depending on concentration, Se can manifest both beneficial and harmful effects on the cell and can have both oxidative and antioxidant effects. Because the therapeutic index for Se is very narrow and it can depend on the form of Se used, we aimed to investigate the potential safety and side effects of inorganic Se on kidney function and structure in rats. After 8 days of treatment, no detectable signs of microscopic changes or oxidative stress in kidney tissue were observed. We detected a moderate increase in urea and creatinine levels in the blood as a sign of a slight decrease in kidney function. The most notable changes in our study were morphometric alterations in proximal tubules and glomeruli, both of which were considerably enlarged. The short-term application of inorganic Se to rats in a supratherapeutic dose induced mild functional and ultrastructural changes in the kidneys. The dose of inorganic Se used could be considered relatively safe for short-term application in situations where Se could be beneficial to the organism, such as the usage of known nephrotoxicants or high levels of oxidative stress in the body.

CD38 deficiency prevents diabetic nephropathy by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Diabetic nephropathy (DN) is one of the most common complications of diabetes. Our previous study showed that CD38 knockout (CD38KO) mice had protective effects on many diseases. However, the roles and mechanisms of CD38 in DN remain unknown. Here, DN mice were generated by HFD feeding plus streptozotocin (STZ) injection in male CD38KO and CD38flox mice. Mesangial cells (SV40 MES 13 cells) were used to mimic the injury of DN with palmitic acid (PA) treatment in vitro. Our results showed that CD38 expression was significantly increased in kidney of diabetic CD38flox mice and SV40 MES 13 cells treated with PA. CD38KO mice were significantly resistant to diabetes-induced renal injury. Moreover, CD38 deficiency markedly decreased HFD/STZ-induced lipid accumulation, fibrosis and oxidative stress in kidney tissue. In contrast, overexpression of CD38 aggravated PA-induced lipid accumulation and oxidative stress. CD38 deficiency increased expression of SIRT3, while overexpression of CD38 decreased its expression. More importantly, 3-TYP, an inhibitor of SIRT3, significantly enhanced PA-induced lipid accumulation and oxidative stress in CD38 overexpressing cell lines. In conclusion, our results demonstrated that CD38 deficiency prevented DN by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Rehmapicrogenin attenuates lipopolysaccharide-induced podocyte injury and kidney dysfunctions by regulating nuclear factor E2-related factor 2/antioxidant response element signalling.

Apoptosis and oxidative stress in kidneys are critical players in acute kidney injury (AKI). Rehmapicrogenin, a monomeric compound extracted from Rehmanniae radix, has been found to possess nitric oxide inhibitory and anti-inflammatory activities. Thus, this study aimed to investigate the roles and mechanisms of rehmapicrogenin in AKI. Lipopolysaccharide (LPS) was used to induce AKI-like conditions. Cell survival conditions were detected by cell counting kit-8 assays and flow cytometry. Several renal function markers including blood urea nitrogen, proteinuria, creatinine, and albumin were measured. Apoptosis and reactive oxygen species (ROS) production were examined by TUNEL and dihydroethidium staining, respectively. Haematoxylin-eosin staining and periodic acid-Schiff staining were conducted to assess histopathological changes. Gene expression was evaluated by western blotting, commercially available kits and immunofluorescence staining. For in vitro analysis, rehmapicrogenin inhibited the LPS-induced podocyte apoptosis by activating the Nrf2/ARE pathway. For in vivo analysis, rehmapicrogenin improved renal functions in LPS-induced mice. Additionally, rehmapicrogenin suppressed LPS-induced podocyte apoptosis and oxidative stress in kidney tissues. Mechanistically, rehmapicrogenin activated the Nrf2/ARE pathway in LPS-induced mice. Rehmapicrogenin relieves the podocyte injury and renal dysfunctions through activating the Nrf2/ARE pathway to inhibit apoptosis and oxidative stress.

Renal Fibrosis and Oxidative Stress Induced by Silica Nanoparticles in Male Rats and Its Molecular Mechanisms.

The utilization of amorphous silica nanoparticles (SiNPs) is gaining popularity in various applications, but it poses a potential risk to human and environmental health. However, the underlying causes and mechanisms of SiNPs-induced kidney damage are still largely unknown. This study aimed to investigate the SiNPs-induced damage in the kidney and further explore the possible mechanisms of SiNPs-induced nephrotoxicity. Thirty adult male rats were divided into 3 different groups. Rats in groups 2 and 3 were administered SiNPs at 2 dosage levels (25 and 100 mg/kg of body weight), while the rats in the control group received no treatment for 28 days. Reactive oxygen species (ROS), antioxidant enzyme activities (glutathione peroxidase [GPx], superoxide dismutase [SOD], and catalase [CAT]), glutathione (GSH) levels, and oxidation markers (such as lipid peroxidation [malondialdehyde (MDA)] and protein oxidation [protein carbonyl (PCO)]) were analyzed in the kidney tissue. Additionally, renal fibrogenesis was studied through histopathological examination and the expression levels of fibrotic biomarkers. The findings revealed that in vivo treatment with SiNPs significantly triggered oxidative stress in kidney tissues in a dose-dependent manner. This was characterized by increased production of ROS, elevated levels of MDA, PCO, and nitric oxide (NO), along with a significant decline in the activities of SOD, CAT, GPx, and reduced GSH. These changes were consistent with the histopathological analysis, which indicated interstitial fibrosis with mononuclear inflammatory cell aggregation, tubular degeneration, glomerulonephritis, and glomerular atrophy. The fibrosis index was confirmed using Masson's trichrome staining. Additionally, there was a significant upregulation of fibrosis-related genes, including transforming growth factor-beta 1 (TGF-β1), matrix metalloproteinases 2 and 9 (MMP-2/9), whereas the expression of tissue inhibitor of metalloproteinase 2 (TIMP2) was downregulated. This study provided a new research clue for the role of ROS and deregulated TGF-β signaling pathway in SiNPs nephrotoxicity.

The effect of N-acetylcysteine use against ER stress in kidney tissue of obese rats

Endoplasmic reticulum (ER) stress has recently gained increasing importance in the pathogenesis of obesity-associated kidney disease. N-acetylcysteine (NAC) is an antioxidant that acts directly and indirectly through upregulating cellular antioxidants. This study's obesity model was created using a high-fat (60% k/cal) diet. NAC (150 mg/kg) was administered by intragastric gavage for eight weeks in both the NAC and obesity + NAC (ObNAC) groups. GRP78 and PERK expressions were determined immunohistochemically in sections taken from kidney tissues obtained at the end of the experiment. The H score of GRP78 was significantly higher in the Ob group than in the Cont, NAC, and ObNAC groups (p 0.05). The PERK H score of the Ob group was also significantly higher than the Cont, NAC, and ObNAC groups (p

Antioxidant and Anti-inflammatory Effects of α-Lipoic Acid on Lipopolysaccharide-induced Oxidative Stress in Rat Kidney

α-Lipoic acid (α-LA) is a naturally occurring organosulfur component. Oxidative stress plays an essential role in the pathogenesis of various diseases, such as kidney and cardiovascular diseases, diabetes, neurodegenerative disorders, cancer and aging. Kidneys are especially vulnerable to oxidative stress and damage. The aim of the study was to evaluate the effect of α-LA on lipopolysaccharide (LPS)-induced oxidative stress parameters in rat kidneys. The experimental rats were divided into four groups: I—control (0.9% NaCl i.v.); II—α-LA (60 mg/kg b.w. i.v.); III—LPS (30 mg/kg b.w. i.v.); and IV—LPS + LA (30 mg/kg b.w. i.v. and 60 mg/kg b.w. i.v., respectively). In kidney homogenates the concentration of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), sulfhydryl groups (−SH), total protein, superoxide dismutase (SOD), total glutathione (tGSH), reduced glutathione (GSH), glutathione disulphide (GSSG) and the GSH/GSSG ratio were determined. In addition, the levels of tumour necrosis factor (TNF)-α, and interleukin (IL)-6 were measured to assess inflammation and was estimated kidney oedema. Studies have shown that α-LA administered after LPS administration attenuated kidney oedema and significantly decreased TBARS, H2O2, TNF-α, and IL-6 levels in rat kidneys. α-LA also resulted in increase −SH group, total protein, and SOD levels and ameliorated the GSH redox status when compared to the LPS group. The results suggest that α-LA plays an important role against LPS-induced oxidative stress in kidney tissue as well as downregulating the expression of pro-inflammatory cytokines.Graphical

Effect of L-serine on oxidative stress markers in the kidney of streptozotocin-induced diabetic mice.

Oxidative stress is critical in the occurrence and development of diabetes and its related complications. L-serine has recently been shown to reduce oxidative stress, the incidence of autoimmune diabetes and improve glucose homeostasis. The aim of this study was to investigate the effects of daily L-serine administration on blood glucose, renal function and oxidative stress markers in the kidney of streptozotocin-induced diabetic mice. Eighteen C57BL/6 male mice were randomly divided into three groups (n = 6 per group). Streptozotocin was used to induce diabetes and a group of diabetic mice was treated with 280mg/day of L-serine dissolved in drinking water for 4weeks. The level of blood glucose, biochemical markers of renal function (total protein, urea, creatinine and albumin) and oxidative stress markers (protein carbonyls, malondialdehyde, glutathione peroxidase, superoxide dismutase and catalase) were measured using spectrophotometry. The results indicated that L-serine significantly decreased the glucose level in diabetic mice (188.6 ± 22.69mg/dL, P = 0.02). Moreover, treatment of diabetic mice with L-serine reduced protein carbonyls (3.249 ± 0.9165nmol/mg protein, P < 0.05) and malondialdehyde levels (1.891 ± 0.7696μM/mg protein, P = 0.051). However, L-serine showed no significant effects on renal function, and a slight reduction in histopathological changes was observed in mice receiving L-serine. This study revealed that L-serine effectively ameliorates oxidative stress in kidney tissue and reduces the blood glucose concentration in diabetic mice.

Gallic acid improves the metformin effects on diabetic kidney disease in mice

Objectives Metformin is an antidiabetic agent that is used as the first-line treatment of type 2 diabetes mellitus. Gallic acid is a type of phenolic acid that has been shown to be a potential drug candidate to treat diabetic kidney disease, an important complication of diabetes. We aimed to test whether a combination of gallic acid and metformin can exert synergetic effect on diabetic kidney disease in diabetic mice model. Methods Streptozotocin (65 mg/kg) intraperitoneal injection was used to induce diabetic kidney disease in mice. The diabetic mice were treated with saline (Vehicle), gallic acid (GA) (30 mg/kg), metformin (MET) (200 mg/kg), or the combination of gallic acid (30 mg/kg) and metformin (200 mg/kg) (GA + MET). Results Our results demonstrated that compared to the untreated diabetic mice, all three strategies (GA, MET, and GA + MET) exhibited various effects on improving renal morphology and functions, reducing oxidative stress in kidney tissues, and restoring AMP-activated protein kinase (AMPK)/silent mating type information regulation 2 homolog 1 (SIRT1) signaling in kidney tissues of diabetic mice. Notably, the combination strategy (GA + MET) provided the most potent renal protection effects than any single strategies (GA or MET). Conclusion Our results support the hypothesis that gallic acid might serve as a potential supplement to metformin to enhance the therapeutical effect of metformin.

Punica granatum L. Polyphenolic Extract as an Antioxidant to Prevent Kidney Injury in Metabolic Syndrome Rats.

Obesity and metabolic syndrome (MetS) constitute a rapidly increasing health problem and contribute to the development of multiple comorbidities like acute and chronic kidney disease. Insulin resistance, inappropriate lipolysis, and excess of free fatty acids (FFAs) are associated with glomerulus hyperfiltration and atherosclerosis. The important component of MetS, oxidative stress, is also involved in the destabilization of kidney function and the progression of kidney injury. Natural polyphenols have the ability to reduce the harmful effect of reactive oxygen and nitrogen species (ROS/RNS). Extract derived from Punica granatum L. is rich in punicalagin that demonstrates positive effects in MetS and its associated diseases. The aim of the study was to investigate the effect of bioactive substances of pomegranate peel to kidney damage associated with the MetS. In this study, we compared biomarkers of oxidative stress in kidney tissue of adult male Zucker Diabetic Fatty (ZDF) rats with MetS and healthy controls that were treated with Punica granatum L. extract at a dose of 100 or 200 mg/kg. Additionally, we evaluated the effect of polyphenolic extract on kidney injury markers and remodeling. The concentration of ROS/RNS, oxLDL, glutathione (GSH), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), metalloproteinase 2 and 9 (MMP-2, MMP-9), and the activity of superoxide dismutase (SOD) and catalase (CAT) were measured. The data showed significant differences in oxidative stress markers between treated and untreated MetS rats. ROS/RNS levels, oxLDL concentration, and SOD activity were lower, whereas CAT activity was higher in rats with MetS receiving polyphenolic extract. After administration of the extract, markers for kidney injury (NGAL, KIM-1) decreased. Our study confirmed the usefulness of pomegranate polyphenols in the treatment of MetS and the prevention of kidney damage. However, further, more detailed research is required to establish the mechanism of polyphenol protection.

AST-120 to Target Protein-Bound Uremic Toxins Improves Cardiac Output and Kidney Oxygenation in Experimental Chronic Kidney Disease

Introduction: Chronic kidney disease (CKD) is a global health problem with increasing incidence which is closely associated with cardiac dysfunction. In CKD, uremic toxins accumulate as kidney function declines. Additionally, high salt intake is a growing health issue worldwide which can exacerbate kidney disease. In this study, we investigated the effect of reducing plasma levels of protein-bound uremic toxins in a rat model of CKD, challenged with high salt intake and compared the effects to those of conventional treatment using an angiotensin-converting enzyme inhibitor (ACEI). Methods: In rats, the right kidney and 2/3 of the left kidney were surgically removed (5/6 nephrectomy). Animals were fed a normal-salt diet and randomized to either no treatment (control) or chronic treatment with either the oral absorbent AST-120 to reduce plasma levels of protein-bound uremic toxins or the ACEI enalapril to inhibit angiotensin II signaling for 5 weeks. Following treatment, kidney function was measured before and after a week of high salt intake. Cardiac output and markers of oxidative stress were measured at the end of the study period. Results: Treatment with AST-120 resulted in decreased levels of the uremic toxin indoxyl sulfate, improved cardiac output (mL/min: AST-120 44.9 ± 5.4 compared to control 26.6 ± 2.0; p < 0.05), and decreased urinary oxidative stress. ACEI reduced oxidative stress in kidney tissue and improved the glomerular filtration rate in response to high salt intake (mL/min: ACEI 1.5 ± 0.1; compared to control 1.1 ± 0.1; p < 0.05). Both interventions improved intrarenal oxygen availability (mm Hg: AST-120 42.8 ± 0.8; ACEI 43.2 ± 1.9; compared to control 33.4 ± 1.3; p < 0.05). Conclusion: AST-120 administered to reduce plasma levels of uremic toxins, such as indoxyl sulfate, has potential beneficial effects on both cardiac and kidney function. Targeting uremic toxins and angiotensin II signaling simultaneously could be an efficient strategy to target both cardiac and kidney dysfunction in CKD, to further slow progression of disease in patients with CKD.

Silimarin’in Paklitaksel Kaynaklı Nefrotoksisiteye Karşı Koruyucu Etkileri

The effects of drugs used in cancer treatment are not only specific to cancer cells but also negatively affect healthy cells. This study, it was aimed to investigate the protective effects of silymarin (SLY), which stands out with its antioxidant effects, against the possible harmful effects of paclitaxel (PAX), an anticancer drug, on kidney tissue. A total of 28 Sprague-Dawley female rats were randomly selected into four groups (n=7): Control, PAX, SLY, and PAX + SLY. PAX was administered 2 mg/kg to the PAX group by intraperitoneally (i.p.); SLY was administered 100 mg/kg to the SLY group by oral gavage. Also, The PAX + SLY group was administered the same dose and route of PAX and SLY as the previous groups. In the biochemical analyzes performed in blood and kidney tissues taken from animals at the end of the experimental procedures, it was determined that PAX increased oxidative stress in kidney tissue and creatinine (Cr) and blood urea nitrogen (BUN) levels in serum. In the histopathological examinations of the kidney tissue, it was observed that PAX caused pathological changes such as renal corpuscle atrophy, damage to the brush border, vacuolar degeneration, and desquamation. The administration of SLY, a pharmacological agent with anti-inflammatory, anti-apoptotic, and antioxidant effects, largely prevented these pathological changes that occurred as a result of PAX use. The results obtained in the current study showed that SLY can be used as a protective agent against harmful effects on kidney tissue in treatments with PAX.

Silymarin protects the rats against paraquat-induced acute kidney injury via Nrf2.

Paraquat (PQ) poisoning induces severe acute kidney injury and causes extremely high rate of death. In this study, we aimed to investigate the protective effects of silymarin on PQ-induced acute kidney injury and explore the underlying mechanisms. A rat model was established through intraperitoneal injection of PQ. Rats were administrated with saline or silymarin for 3days. Then, survival rate, physiological parameters, and renal injury score were evaluated. The apoptosis and oxidative stress in kidney tissues were determined through hematoxylin and eosin staining, quantitative reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assays. Silymarin administration could significantly increase the survival rate of PQ-poisoned rats. It was found that silymarin treatment improved renal function, decreased injury score in kidney tissues, and inhibited the apoptosis and oxidative stress in PQ-induced acute kidney injury through the activating the signaling pathway of Nrf2 and promoting its nuclear translocation. Silymarin exhibited a protective effect against PQ-induced kidney injury, suggesting that treatment with this flavonoid could be a potential therapeutic agent for the treatment of acute kidney injury.

Impact of high salt diets on CHOP-mediated apoptosis and renal fibrosis in a rat model.

Prolonged and excessive salt intake accelerates oxidative stress in kidney tissues, which brings about ER stress. The PERK/ATF4/CHOP/BCL-2 signaling pathway has an essential role in ER stress-induced apoptosis. The present study aimed to investigate the effect of high salt diets on the development of renal fibrosis through CHOP-mediated apoptosis. Twenty-five male Wistar rats were randomly divided into five groups (n = 5 each). Groups 1-5 were treated with 0%, 0.5%, 1%, 1.2%, 1.5% of NaCl dissolved in distilled water, respectively, for 8weeks. To detect the degree of renal tubular damage, urinary KIM-1 was measured. The slides of renal tissues were stained via Masson's Trichrome staining methods for fibrosis detection. The relative gene expression of ATF4, CHOP, and BCl-2 in renal tissues were analyzed using the qRT-PCR method. The results revealed no significantdifference between the urea, creatinine, and urine flow rate of the rats receiving different concentrations of NaCl (groups 2-5) and those of the control group (group 1). The rats treated with 1.5% NaCl (group 5) showed significant elevations in urinary KIM-1 and the mRNA level of CHOP compared to the control group. Mild renal fibrosis was also observed in group 5. Excessive salt intake leads to fibrosis as it induces the PERK/ATF4/CHOP/BCL-2 signaling pathway in renal tissues. KIM-1 is detectable in urine before the impairment of renal function which can be used as a diagnostic marker to prevent the development of progressive renal failure.

MiR-494-mediated Effects on the NF-κB Signaling Pathway Regulate Lipopolysaccharide-Induced Acute Kidney Injury in Mice

ABSTRACT Objective To explore the effects of miR-494 inhibition through the NF-κB signaling pathway on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) mouse model. Methods The AKI mice induced by LPS were treated with miR-494 antagomir, and the kidney parameters and indicators of oxidative stress were detected. HE and TUNEL staining were performed to observe the kidney histopathology and the apoptosis in renal tubular epithelial cells (RTECs), respectively. The ROS level was measured using dihydroethidium (DHE) staining. In addition, qRT-PCR, western blotting, immunohistochemistry (IHC), and ELISA were also used to detect gene or protein expression. Results LPS-induced AKI mice injected with the miR-494 antagomir showed reduced blood urea nitrogen (BUN) and serum creatinine (Cr) with improved kidney histopathology. The expression levels of p-IKKα/β, p-IκBα and p65 NF-κB in the nucleus were increased in kidney tissues from the LPS-induced AKI mice, and they were decreased by the miR-494 antagomir. Moreover, the results of IHC showed that the miR-494 antagomir downregulated p65 NF-κB in kidney tissues from the LPS-induced AKI mice, accompanied by decreased levels of TNF-α, IL-1β, IL-6, MDA, NO, and ROS but increased levels of SOD and GSH. In addition, the LPS-induced AKI mice had increased apoptosis in RTECs, as well as increased Caspase-3 and Bax and decreased Bcl-2, which were reversed by the miR-494 antagomir. Conclusions The inhibition of miR-494 could reduce inflammatory responses and improve oxidative stress in kidney tissues from LPS-induced AKI mice by blocking the NF-κB pathway accompanying by reduced apoptosis in RTECs.

Effects of Nigella sativa oil and thymoquinone on radiation-induced oxidative stress in kidney tissue of rats

Ionizing radiation leads to release of free radicals into the systemic circulation from irradiated tissues. These free radicals cause oxidative stress in distant organs. Oxidative status may be reversed by naturally occurring antioxidant agents. The aim of this study was to investigate protective and antioxidant effects of Nigella sativa oil (NSO) and thymoquinone (TQ) in kidney tissue of rats exposed to cranial irradiation. Forty-eight Sprague-Dawley rats were divided into six groups: IR group received irradiation (IR) to total cranium plus saline; IR plus NSO group received IR and NSO; IR plus TQ group received IR and TQ; sham group did not receive NSO, TQ or IR; control group of TQ received dimethyl sulfoxide; control group of NSO received saline. Total oxidant status (TOS), oxidative stress index (OSI) and lipid hydroperoxide (LOOH) levels were studied as oxidative parameters, and total antioxidant status (TAS), total sulfhydryl levels, paraoxonase (PON), ceruloplasmin (Cp) and arylesterase activities were determined as antioxidative parameters in the kidney tissue of rats. Kidney TOS, OSI and LOOH levels were significantly lower in IR plus TQ, IR plus NSO and sham groups compared to IR group (p < 0.001). TAS, PON and Cp activities in IR group were significantly lower compared to the control group (p < 0.001). PON and Cp activities were significantly higher in IR plus NSO and IR plus TQ groups compared to IR group (p < 0.001). In conclusion, free radicals generated by cranial ionizing radiation exposure cause oxidative stress in kidney. NSO and TQ exhibit protective and antioxidant effects against oxidative damage in rats.

Long-Term Angiotensin II Infusion Induces Oxidative and Endoplasmic Reticulum Stress and Modulates Na+ Transporters Through the Nephron.

High plasma angiotensin II (Ang II) levels are related to many diseases, including hypertension, and chronic kidney diseases (CKDs). Here, we investigated the relationship among prolonged Ang II infusion/AT1 receptor (AT1R) activation, oxidative stress, and endoplasmic reticulum (ER) stress in kidney tissue. In addition, we explored the chronic effects of Ang II on tubular Na+ transport mechanisms. Male Wistar rats were subjected to sham surgery as a control or prolonged Ang II treatment (200 ng⋅kg–1⋅min–1, 42 days) with or without losartan (10 mg⋅kg–1⋅day–1) for 14 days. Ang II/AT1R induced hypertension with a systolic blood pressure of 173.0 ± 20 mmHg (mmHg, n = 9) compared with 108.0 ± 7 mmHg (mmHg, n = 7) in sham animals. Under these conditions, gene and protein expression levels were evaluated. Prolonged Ang II administration/AT1R activation induced oxidative stress and ER stress with increased Nox2, Nox4, Cyba and Ncf1 mRNA expression, phosphorylated PERK and eIF2α protein expression as well as Atf4 mRNA expression. Ang II/AT1R also raised Il1b, Nfkb1 and Acta2 mRNA expression, suggesting proinflammatory, and profibrotic effects. Regarding Na+ tubular handling, Ang II/AT1R enhanced cortical non-phosphorylated and phospho/S552/NHE3, NHE1, ENaC β, NKCC2, and NCC protein expression. Our results also highlight the therapeutic potential of losartan, which goes beyond the antihypertensive effect, playing an important role in kidney tissue. This treatment reduced oxidative stress and ER stress signals and recovered relevant parameters of the maintenance of renal function, preventing the progression of Ang II-induced CKD.

Effect of Exercise on Oxidant and Antioxidant Systems in Rat Kidney Tissue with Hyperthyroidism

Oxidative stress is involved in the pathogenesis of many diseases. Hyperthyroidism is associated with increased oxidative tissue damage. The aim of this study is to investigate whether if there is any protective effect of a regular endurance exercise on oxidative stress in kidney tissues of rats with experimental hyperthyroidism. Twenty-three male Spraque Dawley rats were divided into four groups: Control, hyperthyroid, exercise and, hyperthyroid with exercise. Hyperthyroid was induced in rats by subcutaneous injections at a dosage of 250 µg L-thyroxine per kg body weight and hyperthyroidism was confirmed by the measurements of TSH, FT 3 and FT 4 in serum. Endurance training lasted 8 weeks and consisted of 45 minutes daily treadmill running at a speed of 23 m/minute for 5 days a week. The levels of MDA, GSH and, GSH-Px activity were measured in kidney homogenates. MDA level of the hyperthyroid group was significantly higher than those of the control group(p=0.022). On the other hand, the MDA level of the exercise group was significantly lower than the MDA level of the hyperthyroid group (p=0,001). GSH level and GSH-Px activities were lower in the hyperthyroid group comparing the control group (p<0.05). GSH level and GSH-Px activity in the exercise group were higher than compared with the hyperthyroid group (p<0.05). The results of our study show that L-thyroxine injection may increase oxidative stress by causing lipid peroxidation at kidney tissues and endurance training may decrease oxidative stress. Keywords: Endurance training, glutathione, glutathione peroxidase, hyperthyroidism, kidney tissue, malondialdehyde DOI: 10.7176/JMPB/70-05 Publication date: April 30 th 2021

Protective effect of coenzyme Q10 nanoparticles against monocrotophos induced oxidative stress in kidney tissues of rats

The present study evaluated the effect of coenzyme Q10 nanoparticles (CoQ NPs) against monocrotophos (MCP) exposure-induced oxidative stress in kidney tissue of rats. Albino wistar rats were divided into four groups i.e. control, CoQ NPs-treated, MCP-treated and MCP + CoQ NPs-treated groups. An acute dose of MCP (4.5 mg/kg b.wt) dissolved in corn oil was administered while CoQ NPs were given at a dose of 100 mg/kg b.wt 2 h before MCP treatment. Results showed that MCP exposure resulted in oxidative stress generation in kidney tissue of rats as depicted by increased lipid peroxidation and protein oxidation followed by decreased glutathione content in tissue homogenate. The activity of superoxide dismutase also decreased significantly in kidney tissue. Histopathological analysis showed many cellular alterations in the kidney tissue supporting the toxic effects of MCP exposure in rats. Co-treatment of CoQ NPs with MCP significantly ameliorated the oxidative stress generation and improved the histological alterations. The results indicate that CoQ NPs have the potential to reverse the oxidative stress generated after MCP exposure in rat kidneys suggesting their therapeutic potential.

Expression of 4-Hydroxynonenal (4-HNE) and Heme Oxygenase-1 (HO-1) in the Kidneys of Plasmodium berghei-Infected Mice.

Acute kidney injury (AKI) is one of the most serious complications of severe Plasmodium falciparum malaria, but the exact pathogenic mechanisms of AKI in P. falciparum infection have not been clearly elucidated. We hypothesized that oxidative stress is a potential mediator of acute tubular necrosis in P. falciparum-infected kidneys. Therefore, this study aimed to investigate the histopathological changes and markers of oxidative stress in kidney tissues from mice with experimental malaria. DBA/2 mice were divided into two groups: the mice in the malaria-infected group (n = 10) were intraperitoneally injected with 1 × 106P. berghei ANKA-infected red blood cells, and the mice in the control group (n = 10) were intraperitoneally injected with a single dose of 0.85% normal saline. Kidney sections were collected and used for histopathological examination and the investigation of 4-hydroxynonenal (4-HNE) and heme oxygenase-1 (HO-1) expression through immunohistochemistry staining. The histopathology study revealed that the P. berghei-infected kidneys exhibited a greater area of tubular necrosis than those of the control group (p < 0.05). The positive staining scores for 4-HNE and HO-1 expression in tubular epithelial cells of the P. berghei-infected group were significantly higher than those found for the control group (p < 0.05). In addition, significant positive correlations were found between the tubular necrosis score and the positive staining scores for 4-HNE and HO-1 in the kidneys from the P. berghei-infected group. In conclusion, this finding demonstrates that increased expression of 4-HNE and HO-1 might be involved in the pathogenesis of acute tubular damage in the kidneys during malaria infection. Our results provide new insights into the pathogenesis of malaria-associated AKI and might provide guidelines for the future development of a therapeutic intervention for malaria.