Stress In Renal Tissues Research Articles

Exploration on the protective effect of liraglutide on renal injury in diabetic nephropathy rats based on ROS-NLRP3 inflammasomes

Objective: To investigate the effect of liraglutide on diabetic nephropathy in rats and its regulatory mechanism. Methods: The diabetic nephropathy rat model was constructed with high-glucose-high-fat diet in combination with STZ, and was randomly divided into normal saline group and liraglutide group. The rats in liraglutide group were given sc 200 μg/kg of liraglutide, and the rats in normal saline group were given sc 20 mg/kg of normal saline twice a day for 4 weeks. The normal control group was not treated with any treatment. The biochemical indexes such as rat body weight, 24-hour urine total protein quantification (UTP), fasting blood glucose (FPG), triglyceride (TG), cholesterol (TC), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured. HE staining, Masson staining and PAS staining were used to observe the pathologically morphological changes in renal tissues. Western-blot was used to detect the expression of NLRP3 inflammasome-related protein in renal tissues. Elisa was used to measure the serum levels of interleukin-18 (IL-18) and IL-1β. SPSS 26.0 statistical software and Graph Prism 9.0 software were used for analysis and mapping. The t-test was used for the comparison of measurement data between two groups, one-way ANOVA was used for the comparison among multiple groups, and Tukey’s test was used for the comparison in the same group. Results: Compared with the normal saline group, FBG, UTP, BUN, Scr, TC and TG in the liraglutide group were significantly decreased (p < .01), the glomerular basement membrane was slightly thickened, with the tubular lumen slightly dilated and the lesion damage alleviated; the expression levels of NLRP3, ASC and caspase-1 inflammasome-related proteins were decreased (p < .01), and the levels of IL-18 and IL-1β were decreased (p < .01).Conclusion: Liraglutide can inhibit the activation of NLRP3 inflammasome mediated by oxidative stress in renal tissues through ROS-NLRP3 inflammasome pathway, thereby inhibiting the inflammation, and finally playing an anti-diabetic nephropathy renal injury role.

Protective effects of the secondary metabolites from Quercus salicina Blume against gentamicin-induced nephrotoxicity in zebrafish (Danio rerio) model

To reveal the protective effect on the nephrotoxicity of Quercus salicina Blume(QS), a traditional medicine for the treatment of urolithiasis, the 50 % ethanol extract from the branches and leaves of QS was chemically studied by systematic solvent extraction and HPLC chromatography. Two phenolic acids and three flavonoids were identified by nuclear magnetic resonance spectroscopy, namely Ferulic acid (1), p-Hydroxycinnamic acid (2), Hesperidin (3), Formononetin (4), and Quercetin (5). At the same time, the gentamicin-induced nephrotoxicity of zebrafish was used as a model for the first time. The antioxidant activity of these derivatives with good antioxidant activity screened from free radical scavenging experiments in vitro (DPPH and ABTS) was evaluated in vivo, including protein levels (LPO, NO, GSH, and SOD), kidney injury factor (KIM-1), zebrafish kidney pathology and real-time PCR. The results showed that metabolites 1, 3, and 5 had strong antioxidant activity, and oxidative stress in renal tissue was significantly reduced; KIM-1, TNF-α, and IL-6 mRNA expression in a dose-dependent manner, which preliminarily revealed the protective effect of the secondary metabolites of QS on nephrotoxicity, and preliminarily discussed the structure-activity relationship. This study provides an experimental basis for further exploring the mechanism of QS in the kidney.

Baicalin-2-ethoxyethyl ester alleviates gentamicin-induced acute kidney injury via NF-κB signaling pathway

Drug nephrotoxicity has high fatality rates and complications. To study this conditional, traditionally, Gentamicin (GM) is used to induce acute injury and establish a nephrotic syndrome model. Baicalin, a flavonoid derived from baicalin with potent anti-inflammatory and antioxidant activity, has been used to treat various inflammatory diseases. This study aims to investigate the process of baicalin-2-ethoxyethyl ester (BAE) synthesis and its therapeutic effect on GM-induced acute kidney injury (AKI). Briefly, baicalin was processed by various reactions to yield BAE. A GM-induced AKI model was established for in vivo evaluation of the protective effect and mechanism of BAE. The results indicated that BAE reduced serum creatinine and urea nitrogen levels and improved pathological alterations, inflammatory responses, and oxidative stress in renal tissues. Furthermore, it was revealed that BAE might exert anti-inflammatory and anti-oxidative responses during AKI via the NF-κB signaling pathway regulation. The findings imply that BAE has a protective impact on the kidneys and might serve as a potent medicine for treating renal damage.

Aucubin mitigates nonylphenol-induced renal damage by attenuating apoptosis, oxidative stress and histopathological profile

Nonylphenol (NP) is potent noxious pollutant which is documented to induce nephrotoxicity via escalating the levels of oxidative stress in renal tissues. Aucubin (AUC) is a novel phytochemical having tremendous pharmacological abilities. This research aimed to estimate the efficacy of AUC against NP intoxicated renal impairment in male albino rats. 48 albino rats were randomly assigned into four different groups viz. control group, NP administered group (50 mg/kg), NP + AUC administrated (50 mg/kg + 40 mg/kg) group and AUC treated (40 mg/kg) group. Our results showed that NP intoxication raised urinary proteins, creatinine, urea, urobilinogen, NGAL and KIM-1 levels. Besides, NP exposure lowered the levels of creatinine clearance and albumin. Furthermore, NP treatment lowered level of total protein, activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GSR) & glutathione (GSH) contents along with the level of total antioxidant status (TAS) however, raising the oxidative stress markers levels Thiobarbituric acid reactive substance (TBARS), reactive oxygen species (ROS), hydrogen peroxide (H2O2) & total oxidant status (TOS). Additionally, following the NP administration, the levels of Bax, caspase-9, & caspase-3 were augmented however the Bcl-2 level was decreased. Furthermore, rats exposed to NP showed various histopathological disruptions. Whereas treatment with AUC showed a palliative effect against NP-induced renal damage, restoring all alterations to normal levels. Taken together, AUC administration convalesced NP-induced kidney impairment.

Podocin, mTOR, and CHOP dysregulation contributes to nephrotoxicity induced of lipopolysaccharide/diclofenac combination in rats: Curcumin and silymarin could afford protective effect

AimSepsis is a common cause of acute kidney injury (AKI). Lipopolysaccharides (LPS) are the main gram-negative bacterial cell wall component with a well-documented inflammatory impact. Diclofenac (DIC) is a non-steroidal anti-inflammatory drug with a potential nephrotoxic effect. Curcumin (CUR) and silymarin (SY) are natural products with a wide range of pharmacological activities, including antioxidant and anti-inflammatory ones. The objective of this study was to examine the protective impact of CUR and SY against kidney damage induced by LPS/DIC co-exposure. Materials and methodsFour groups of rats were used; control; LPS/DIC, LPS/DIC + CUR, and LPS/DIC + SY group. LPS/DIC combination induced renal injury at an LPS dose much lower than a nephrotoxic one. Key findingNephrotoxicity was confirmed by histopathological examination and significant elevation of renal function markers. LPS/DIC induced oxidative stress in renal tissues, evidenced by decreasing reduced glutathione and superoxide dismutase, and increasing lipid peroxidation. Inflammatory response of LPS/DIC was associated with a significant increase of renal IL-1β and TNF-α. Treatment with either CUR or SY shifted measured parameters to the opposite side. Moreover, LPS/DIC exposure was associated with upregulation of mTOR and endoplasmic reticulum stress protein (CHOP) and downregulation of podocin These effects were accompanied by reduced gene expression of cystatin C and KIM-1. CUR and SY ameliorated LPS/DIC effect on the aforementioned genes and protein significantly. SignificanceThis study confirms the potential nephrotoxicity; mechanisms include upregulation of mTOR, CHOP, cystatin C, and KIM-1 and downregulation of podocin. Moreover, both CUR and SY are promising nephroprotective products against LPS/DIC co-exposure.

Bioactivities and ethnopharmacology of Sesamum indicum L seed oil

Since time immemorial, humans have utilized plants such as sesame (Sesamum indicum L.) to meet their needs and treat illnesses. Sesame oil (SO) is derived from the seeds and serves several therapeutic purposes. The aim of this study was to identify the ethnobotanical indications and proven biological activities of SO. An integrative review was conducted in the PubMed and Cochrane Library databases. The main search strategy included the following health science descriptors: 'World Population,' 'Sesamum,' and 'Pharmacologic Actions,' organized using the Boolean operators 'AND' and 'OR.' Studies were included based on the following criteria: I) Clinical studies on medicinal indications, II) Proven bioactivities, III) In vivo studies, and IV) In vitro studies. Exclusions were made for a) secondary research and b) studies that did not specifically address indications and effects of Sesamum indicum. The risk of research bias will be assessed using the Downs & Black's tool. Thirty-four studies were selected to comprise the final sample of this research. The biological activity of seed oil of sesame is the result of a combination of different chemical components.action in cardiovascular diseases can be attributed to lignans, immunomodulatory and anti-inflammatory activity can be attributed to sesamin and sesamol, respectively. The antioxidants present in the plant can help reduce oxidative stress in renal tissues. The omega-6 fatty acid present in sesame oil, has been associated with neuroprotective properties. Phytosterols, such as β-sitosterol found in the plant, have wound healing activities. Sesame also plays a role in reducing blood cholesterol levels, among other biological activities. This adds commercial value to the product and enables studies that can support the development of new nutritionally and therapeutically valuable medications. These findings contribute to the commercial value of the product and support the conduct of studies that can facilitate the development of new drugs and food products with high nutritional and therapeutic value.

ANTIOXIDANT EFFECT OF GHRELIN ON NICOTINE-INDUCED RENAL TISSUE DAMAGE IN MICE

Background: Ghrelin is an orexiogenic peptide released from stomach. It protects multiple organs of the body by its antioxidant and anti-inflammatory properties. Ghrelin combats oxidative stress by increasing antioxidant enzymes and decreasing lipid peroxidation. This study was done to determine the nephroprotective effect of ghrelin against nicotine induced renal tissue damage in BALB/c mice by estimating tissue antioxidant enzyme levels, namely catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR) and lipid peroxidation marker malondialdehyde (MDA). Methods: This randomized control trial was conducted at Foundation University School of Health Sciences, Islamabad in collaboration with National Institute of Health, Islamabad. Total of 27 male mice from NIH were randomly allocated into 3 groups. Group I (control) received 1 ml/Kg body weight saline, Group II (nicotine only) received 2.5 mg/Kg of body weight nicotine daily and Group III (nicotine plus ghrelin) received nicotine 2.5 mg/Kg body weight each day along with ghrelin 10 ?g/Kg on alternate days for 29 days via intraperitoneal administration. Renal tissue sampling was done on 30th day for estimation of tissue oxidative stress markers through ELISA. Results: Nicotine administration led to significantly increased levels of CAT (p<0.001), SOD (p<0.001), GR (p<0.001), and decreased MDA (p<0.001) levels in group II. Administration of ghrelin along with nicotine in Group III resulted in significant restoration (p<0.001) of antioxidant enzymes (CAT, SOD, GR) and lipid peroxidation (MDA) (p<0.001) levels. Conclusion: Ghrelin acted as a potent antioxidant in nicotine induced oxidative stress in renal tissue suggesting its potential nephroprotective role. Pak J Physiol 2023;19(2):3–5

Essential Oil of Lippia alba Protects Against Ischemic-Reperfusion Acute Kidney Injury

HIGHLIGHTS Essential Oil of Lippia alba treatment reverted ischemia-induced biochemical alterations. Essential Oil of Lippia alba treatment ameliorated renal morphological alterations. Essential Oil of Lippia alba decreased oxidative stress in renal tissue. Essential Oil of Lippia alba reversed the ischemic damage on tubular cells.

Modulation Effects of Eugenol on Nephrotoxicity Triggered by Silver Nanoparticles in Adult Rats.

The use of silver nanoparticles (AgNPs) is expanding. This study evaluates the modulator effect of eugenol (Eug) on AgNP-induced nephrotoxicity in rats. Sixty male rats were separated into six groups: control, Eug, AgNPs low-dose, AgNPs high-dose, Eug + AgNPs low-dose, and Eug + AgNPs high-dose. After 30 days, kidney function, antioxidative and proinflammatory status, histopathological, histomorphometrical, and immunohistochemical assessments were performed. AgNPs markedly induced oxidative stress in renal tissues, characterized by increased levels of blood urea nitrogen, creatinine, uric acid, kidney injury molecule-1, the total oxidant capacity, malondialdehyde, tumor necrosis factor-alpha (TNF-α), and interleukin-6, as well as decreased levels of the total antioxidant capacity, superoxide dismutase, catalase, reduced glutathione, and glutathione peroxidase. Moreover, the normal renal architecture was destroyed, and the thickness of the renal capsules, cortex, and medulla, alongside the diameter and quantity of the normal Malpighian corpuscles and the proximal and distal convoluted tubules were decreased. Immunoreactivity for P53, caspase-3, and TNF-α reactive proteins were significantly increased; however, Bcl-2 immunoreactivity was decreased. Eug reversed most biochemical, histological, histomorphometrical, and immunohistochemical changes in AgNP-treated animals. This study demonstrated that nephrotoxicity in AgNP-treated rats was mitigated by an Eug supplementation. Eug's antioxidant, antiapoptotic, and anti-inflammatory capabilities were the key in modulating AgNPs nephrotoxicity.

Ginsenoside Rg1 Ameliorates Acute Renal Ischemia/Reperfusion Injury via Upregulating AMPKα1 Expression.

Acute renal ischemia/reperfusion (I/R) injury often occurs during kidney transplantation and other kidney surgeries, and the molecular mechanism involves oxidative stress. We hypothesized that ginsenoside Rg1 (Rg1), a saponin derived from ginseng, would protect the renal tissue against acute renal I/R injury by upregulating 5′ adenosine monophosphate-activated protein kinase α1 (AMPKα1) expression and inhibiting oxidative stress. The models of acute anoxia/reoxygenation (A/R) damage in normal rat kidney epithelial cell lines (NRK-52E) and acute renal I/R injury in mice were constructed. The results revealed that pretreatment with 25 μM Rg1 significantly increased NRK-52E viability, decreased lactate dehydrogenase (LDH) activity and apoptosis, suppressed reactive oxygen species generation and oxidative stress, stabilized mitochondrial membrane potential and reduced mitochondria permeability transition pore openness, decreased adenosine monophosphate/adenosine triphosphate ratio, and upregulated the expression of AMPKα1, cytochrome b-c1 complex subunit 2, NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8, and B-cell lymphoma 2, while downregulating BCL2-associated X protein expression. The effects of Rg1 pretreatment were similar to those of pAD/Flag-AMPKα1. After acute renal I/R injury, serum creatinine, blood urea nitrogen, LDH activity, and oxidative stress in renal tissue significantly increased. Rg1 pretreatment upregulated AMPKα1 expression, which protects against acute renal I/R injury by maintaining renal function homeostasis, inhibiting oxidative stress, and reducing apoptosis. Compound C, a specific inhibitor of AMPK, reversed the effects of Rg1. In summary, Rg1 pretreatment upregulated AMPKα1 expression, inhibited oxidative stress, maintained mitochondrial function, improved energy metabolism, reduced apoptosis, and ultimately protected renal tissue against acute renal I/R injury.

Aerobic exercise training combined or not with okra consumption as a strategy to prevent kidney changes caused by metabolic syndrome in Zucker rats.

The complications of Metabolic Syndrome (MetS) include kidney disease, and most dialysis patients are diagnosed with MetS. The benefit of exercise training (ET) for MetS treatment is already well defined in the literature, but the antidiabetic and antihyperlipidemic benefits of okra (O) have been discovered only recently. The aim of this study was to evaluate the effects of O and/or ET supplementation on renal function and histology; serum urea and creatinine value; inflammation (IL-6, IL-10, TNF-α) and oxidative stress in renal tissue. For this, 32 Zucker rats (fa/fa) were randomly separated into four groups of 8 animals each: Metabolic Syndrome (MetS), MetS + Okra (MetS + O), MetS + Exercise Training (MetS + ET), and MetS + Exercise Training and Okra (MetS + ET + O), and 8 Zucker lean (fa/+) rats comprised the Control group (CTL). Okra was administered by orogastric gavage 2x/day (morning and night, 100 mg/kg) and ET performed on the treadmill, at moderate intensity, 1h/day, 5x/week for 6 weeks. Although the renal function was not altered, the animals with MetS showed greater fibrotic deposition accompanied by a worse stage of renal injury, in addition to increased kidney weight. Although all interventions were beneficial in reducing fibrosis, only ET combined with O was able to improve the degree of renal tissue impairment. ET improved the anti-inflammatory status and reduced nitrite levels, but the combination of ET and O was more beneficial as regards catalase activity. Okra consumption alone did not promote changes in inflammatory cytokines and oxidative stress in the kidney. In conclusion, ET combined or not with O seems to be beneficial in preventing the progression of renal disease when renal function is not yet altered.

Maslinic acid activates renal AMPK/SIRT1 signaling pathway and protects against diabetic nephropathy in mice

BackgroundDiabetic nephropathy has been a devastating complication. Clinically, there is an urgent need for nephroprotective agents to delay the onset of diabetic nephropathy and ameliorate its symptoms. Maslinic acid is a pentacyclic triterpene acid with protective effect on multiple organs against oxidative stress and inflammation. In this research, we hypothesized that maslinic acid protects renal function against diabetic nephropathy.MethodsC57BL/6 J male mice administrated with 50 mg/kg of Streptozocin (STZ) daily were used to establish diabetic mouse model (blood glucose levels > 300 mg/dL). Urinary levels of albumin, total proteins, and creatinine were analyzed by an automatic analyzer. H&E staining was used to evaluate renal damage. qRT-PCR and ELISA were performed to investigate the inflammation and oxidative stress in renal tissues. Western blot was used to assess the activation of AMPK signaling.ResultsMaslinic acid treatment alleviated the loss of body weight and blood glucose in diabetic mice. Renal structure and function were protected by maslinic acid in diabetic mice. 20 mg/kg maslinic acid treatment for 8 weeks significantly alleviated the oxidative stress and inflammation in the kidney of diabetic rats. Maslinic acid treatment activated the renal AMPK/SIRT1 signaling pathway.ConclusionMaslinic acid ameliorates diabetic nephropathy and activates the renal AMPK/SIRT1 signaling pathway.

Allicin protects against renal ischemia–reperfusion injury by attenuating oxidative stress and apoptosis

BackgroundStudies have demonstrated that allicin may play critical roles in the procession of ischemia–reperfusion(I/R) injury. The purpose of this study was to investigate the protective effects of allicin on renal I/R injury by attenuating oxidative stress and apoptosis.MethodsTo establish a model of renal I/R, the right kidney underwent 12 h reperfusion after 45 min ischemia, allicin was administered intraperitoneally at concentrations of 40, 50 or 60 mg/kg. NRK-52E cells were treated with allicin at concentrations of 1, 3 or 5 μM in 24 h hypoxia/ 6 h reoxygenation(H/R) treatments. Indicators of HE, oxidative stress, apoptosis were measured to evaluate the effect of aliicin on renal I/R injury.ResultsAllicin protected renal I/R injury by ameliorating histological injury and decreasing the oxidative stress in renal tissues. Meanwhile, allicin significantly downregulated the expression of Bax and caspase-3, upregulated the expression of Bcl-2 in I/R renal tissues and H/R treated NRK-52E cells.ConclusionsAllicin may exert anti-apoptotic and antioxidative effects to promote renal function recovery in I/R renal tissues and H/R treated NRK-52E cells. Taken together, allicin may be a potential novel therapy option for future renal injury protection.

Activation of Sirtuin 1 by Ellagic Acid Ameliorates Cisplatin-Induced Apoptosis, Oxidative Stress and Nephrotoxicity

Background: Cisplatin (Cis) is a chemotherapeutic agent commonly applied in treating different cancers. However, acute renal injury remains a major side effect of Cis that limits its clinical use. Oxidative stress in renal tissues play a key role in Cis-induced toxicity. This research aimed to investigate the impact of ellagic acid (Ella) on Cis-induced apoptotic renal injury and the possible involvement of sirtuin 1 (SIRT1) and oxidative stress as a possible protective mechanism.
 Methods: Twenty-four Sprague Dawley rats were divided into four groups (n=6) and treated as follows. The control (Cont) group (0.9% saline), Ella group (10 mg/kg), Cis group (7.5 mg/kg), Ella + Cis group (10 mg/kg + 7.5 mg/kg). Ella was administered 7 days prior to Cis injection. Seventy-two hours later, the rats were sacrificed, and blood and kidney samples were collected. Biochemical analyses were performed on serum and kidney homogenate. The histopathological and immunohistochemical analyses were performed on the formalin preserved kidneys.
 Results: Ella significantly decreased serum creatinine and urea levels compared to the Cis group. Furthermore, Ella protects the kidney cortex and medulla against most Cis-induced histopathological changes. Ella significantly decreased kidney contents of malondialdehyde (MDA). Moreover, Ella reversed the Cis-induced reduction of kidney antioxidants, including glutathione peroxidase, superoxide dismutase, and catalase. Ella decreased kidney protein expression of both cyclooxygenase-2 (COX-2) and Bax proteins while increased SIRT1 and Bcl2 expression.
 Conclusion: The results revealed a reduction in SIRT1 protein expression in rat renal medullary and cortical tissues following Cis treatment. However, Ella significantly enhanced SIRT1 expression, antioxidants levels, and reduced Cis-induced apoptosis, inflammation, and oxidative stress by increasing the ratio of Bax/Bcl-2 and reducing the expression of COX-2 and MDA, respectively. These findings provide additional evidence of the antioxidant and antiapoptotic effect of Ella in Cis-induced renal toxicity.

HMGB1 signaling-regulated endoplasmic reticulum stress mediates intestinal ischemia/reperfusion-induced acute renal damage

BackgroundIschemia/reperfusion of the intestine often leads to distant organ injury, but the mechanism of intestinal ischemia/reperfusion-induced renal dysfunction is still not clear. The present study aimed to investigate the mechanisms of acute renal damage after intestinal ischemia/reperfusion challenge and explore the role of released high-mobility group box-1 in this process. MethodsIntestinal ischemia/reperfusion was induced in male Sprague-Dawley rats by clamping the superior mesenteric artery for 1.5 hours. At different reperfusion time points, anti−high-mobility group box-1 neutralizing antibodies or ethyl pyruvate were administered to neutralize or inhibit circulating high-mobility group box-1, respectively. ResultsSignificant kidney injury was observed after 6 hours of intestinal reperfusion, as indicated by increased serum levels of urea nitrogen and creatinine, increased expression of neutrophil gelatinase-associated lipocalin, interleukin-6, and MIP-2, and enhanced cell apoptosis, as indicated by cleaved caspase 3 levels in renal tissues. The levels of phosphorylated eIF2ɑ, activating transcription factor 4, and C/EBP-homologous protein (CHOP) were markedly elevated, indicating the activation of endoplasmic reticulum stress in the impaired kidney. High-mobility group box-1 translocated to cytoplasm in the intestine and serum concentrations of high-mobility group box-1 increased notably during the reperfusion phase. Both anti−high-mobility group box-1 antibodies and ethyl pyruvate treatment significantly reduced serum high-mobility group box-1 concentrations, attenuated endoplasmic reticulum stress in renal tissue and inhibited the development of renal damage. Moreover, the elevated expression of receptor for advanced glycation end products in the kidneys after intestinal ischemia/reperfusion was abrogated after high-mobility group box-1 inhibition. ConclusionThese results suggested that high-mobility group box-1 signaling regulated endoplasmic reticulum stress and promoted intestinal ischemia/reperfusion-induced acute kidney injury. High-mobility group box-1 neutralization/inhibition might serve as a pharmacological intervention strategy for these pathophysiological processes.

The double-stranded RNA-dependent protein kinase inhibitor alleviates endoplasmic reticulum stress and alleviates sepsis-induced renal injury.

The double-stranded RNA-dependent protein kinase (PKR) is involved in inflammatory cytokine expression and disease pathogenesis in many conditions. The aim of this study was to explore the role of PKR in sepsis-induced renal tissue injury. Six-week-old C57BL/6J mice received PKR inhibitor (imoxin) and Endoplasmic reticulum (ER) inducer (tunicamycin) 2 hr prior to induction of inflammation via cecal ligation and puncture (CLP). Renal tissues were collected 24 hr after the CLP treatment and protein expression were assessed. The expression of creatinine (Cre) and blood urea nitrogen (BUN) in serum and inflammation factor in tissues was detected by ELISA, and the apoptosis of renal tissue was detected by TUNEL staining. PKR inhibitors reduce the expression of sepsis-induced ER stress in renal tissue, as well as the pathological changes and renal impairment in renal tissue. PKR inhibitors reduce the expression of sepsis-induced inflammatory response and sepsis-induced apoptosis in renal tissue by ER stress. In conclusion, PKR inhibitor alleviates ER stress and alleviates sepsis-induced renal injury.

Pentoxifylline mitigates cholestasis-related cholemic nephropathy

Aim of the studyCholestasis is the stoppage of bile flow that primarily affects liver function. On the other hand, kidneys are also severely influenced during cholestasis. Cholestasis-induced kidney injury is known as cholemic nephropathy (CN). There is no precise pharmacological option in CN. Previous studies revealed that oxidative stress plays a crucial role in the pathogenesis of CN. On the other hand, the positive effects of pentoxifylline (PTX) against renal injury with different etiologies have been frequently reported. In the current study, the potential nephroprotective role of PTX in cholestasis-induced renal injury is investigated.Material and methodsBile duct ligated (BDL) rats were treated with PTX (10, 50, and 100 mg/kg), and renal markers of oxidative stress, urine level of inflammatory cytokines, as well as renal histopathological alterations were monitored.ResultsSignificant changes in oxidative stress markers were detected in the BDL group. On the other hand, it was found that PTX (10, 50, and 100 mg/kg) significantly ameliorated cholestasis-induced oxidative stress in renal tissue. Renal histopathological changes, including interstitial inflammation, tubular atrophy, fibrosis, and cast formation, were detected in the BDL rats. Moreover, urine pro-inflammatory cytokines [interleukin (IL)-1, IL-9, IL-18, tumor necrosis factor α (TNF-α), and interferon γ (INF-γ)] were significantly increased in the cholestatic animals. PTX (10, 50, and 100 mg/kg, 14 days) significantly ameliorated renal histopathological alterations and urine levels of inflammatory cytokines.ConclusionsThese data indicate a potential nephroprotective role for PTX in cholestasis. The effects of PTX on oxidative stress parameters and the inflammatory response could play a primary role in its renoprotective mechanisms.

Effects of liposomal form of phosphatidylcholine on oxidative-nitrosative stress in renal tissues of rats in burn disease

This experiment carried out on 77 white Wistar rats aimed at studying the effects of liposomal form of phosphatidylcholine (lipin) on oxidative-nitrosative stress in renal tissues in burn disease (BD). This condition was modelled by immersing the epilated skin surface of the hind limb of the experimental animals into hot water (t + 70 –75°C) under light ether anaesthesia for 7 s that led to the development of III A-B degree burns. Lipin was administered intraperitoneally daily in a dose of 50 mg / kg immediately after BD modelling.The research has demonstrated BD modelling is accompanied by the development of oxidative-nitrosative stress in renal tissues as evidenced by a significant increase in the superoxide anion radical production by various sources (endoplasmic reticulum and NO synthase, mitochondrial respiratory chain, leukocyte NADPH oxidase); by the growth in the activity of inducible isozyme of NO-synthase (in the stage of burn shock in 2.83 times, р<0.001) with a decline in the constitutive isoforms activity, by the rise in the concentration of peroxynitrite (in the stage of burn shock in 3.18 times, in the stage of septicotoxemia in 2.56 times).The administration of lipin significantly limits the development of oxidative-nitrosative stress in renal tissues in the dynamics of experimental BD, as evidenced by a probable decrease in superoxide anion radical, NO-synthase activity due to its inducible isoform (in the stage of burn shock – by 35.9%; in the stage of toxemia – by 43.1%, p<0.001), by redressing the imbalance between inducible and constitutive isozymes of NO-synthase, by reducing the concentration of peroxynitrite (in the stage of burn shock – by 34.3%, in the stage of late toxemia – by 44.3%; in the stage of septicotoxemia – by 44.3%, p<0.001).

Effects of Sodium\u2013Glucose Co-transporter 2 Inhibition with Empaglifozin on Renal Structure and Function in Non-diabetic Rats with Left Ventricular Dysfunction After Myocardial Infarction

BackgroundThe use of sodium–glucose co-transporter 2 inhibitors (SGLT2i) is currently expanding to cardiovascular risk reduction in non-diabetic subjects, but renal (side-)effects are less well studied in this setting.MethodsMale non-diabetic Sprague Dawley rats underwent permanent coronary artery ligation to induce MI, or sham surgery. Rats received chow containing empagliflozin (EMPA) (30 mg/kg/day) or control chow. Renal function and electrolyte balance were measured in metabolic cages. Histological and molecular markers of kidney injury, parameters of phosphate homeostasis and bone resorption were also assessed.ResultsEMPA resulted in a twofold increase in diuresis, without evidence for plasma volume contraction or impediments in renal function in both sham and MI animals. EMPA increased plasma magnesium levels, while the levels of glucose and other major electrolytes were comparable among the groups. Urinary protein excretion was similar in all treatment groups and no histomorphological alterations were identified in the kidney. Accordingly, molecular markers for cellular injury, fibrosis, inflammation and oxidative stress in renal tissue were comparable between groups. EMPA resulted in a slight increase in circulating phosphate and PTH levels without activating FGF23–Klotho axis in the kidney and bone mineral resorption, measured with CTX-1, was not increased.ConclusionsEMPA exerts profound diuretic effects without compromising renal structure and function or causing significant electrolyte imbalance in a non-diabetic setting. The slight increase in circulating phosphate and PTH after EMPA treatment was not associated with evidence for increased bone mineral resorption suggesting that EMPA does not affect bone health.

The protective effect of hesperidin against renal ischemia-reperfusion injury involves the TLR-4/NF-κB/iNOS pathway in rats.

Renal injury is reported to have a high mortality rate. Additionally, there are several limitations to current conventional treatments that are used to manage it. This study evaluated the protective effect of hesperidin against ischemia/reperfusion (I/R)-induced kidney injury in rats. Renal injury was induced by generating I/R in kidney tissues. Rats were then treated with hesperidin at a dose of 10 or 20 mg/kg intravenously 1 day after surgery for a period of 14 days. The effect of hesperidin on renal function, serum mediators of inflammation, and levels of oxidative stress in renal tissues were observed in rat kidney tissues after I/R-induced kidney injury. Moreover, protein expression and mRNA expression in kidney tissues were determined using Western blotting and RT-PCR. Hematoxylin and eosin (H&E) staining was done for histopathological observation of kidney tissues. The data suggest that the levels of blood urea nitrogen (BUN) and creatinine in the serum of hesperidin-treated rats were lower than in the I/R group. Treatment with hesperidin also ameliorated the altered level of inflammatory mediators and oxidative stress in I/R-induced renal-injured rats. The expression of p-IκBα, caspase-3, NF-κB p65, Toll-like receptor 4 (TLR-4) protein, TLR-4 mRNA, and inducible nitric oxide synthase (iNOS) was significantly reduced in the renal tissues of hesperidin-treated rats. Histopathological findings also revealed that treatment with hesperidin attenuated the renal injury in I/R kidney-injured rats. In conclusion, our results suggest that hesperidin protects against renal injury induced by I/R by involving TLR-4/NF-κB/iNOS signaling.