Changes In Rat Kidney Research Articles

Temporal Assessment of Gadolinium Deposition and T1 Signal Intensity Changes in Rat Kidney with Single and Multiple Doses of Injection: An Experimental Study.

Gadolinium deposition in biological tissues was first reported in patients with renal failure. We aimed to investigate gadolinium deposition in the rat kidney after exposure to single and multiple doses of gadolinium and evaluate deposition for 1- and 3-month periods. We also aimed to determine any correlation between the amount of deposition and T1-weighted image intensity. Seventy rats (5 animals per group) were included in the sample, and 9 groups received a single dose (0.3, 0.6, and 1.2 mmol/kg) of gadolinium, and 1 group for each dose was sacrificed at the end of the first day, week, and month. Four groups received weekly doses (0.3 and 0.6 mmol/kg) and were sacrificed at the end of 6 and 12 weeks. Measurement of T1 intensities was carried out with postinjection images before sacrifice, and deposition was determined using inductively coupled plasma mass spectrometry. The number of injections was associated with increased gadolinium deposition (P <.001) in the kidney. After the weekly injections, the deposited gadolinium levels did not significantly difer between the low and medium doses at the end of the sixth week (P=.067). There was no agreement between the observers regarding the measurement of T1 signal intensity in both single-dose and multidose experiments (P=.263 and P=.307, respectively). Deposition was dose dependent in the postinjection stage in contrast to the late stage in which deposition was not associated with dose or number of injections until the 12th week. T1 signal intensity measurement is unreliable for assessing deposition in the rat kidney.

Evaluation of the changes induced by tramadol and the possible protective effect of vitamin C on the kidney.

Addiction is a widespread public health problem despite all efforts to prevent and treat it. Over the past few years, tramadol abuse has been sharply increasing in Middle Eastern countries. This research aims to identify the tramadol-induced histological changes in rat kidneys and any potential protective effects of vitamin C on these changes. This is an experimental study conducted at Prince Sattam bin Abdul Aziz University. Thirty-three adult albino rats were randomly divided into three groups. Control, Tramadol, and vitamin C groups. The Tramadol group received 25 mg/ Kg a day of tramadol orally via gastric gavage for three weeks. In the vitamin C + tramadol treated group, 100 mg/Kg/b.wt of vitamin C was administered intravenously to the animals 30 minutes before receiving the same dose of tramadol RESULTS: Specimens from the kidney of every rat were excised for histological examination by the light and electron microscope. Tramadol damage to the kidney's glomeruli and proximal and distal convoluted tubule hypertrophy were among its long-term harmful consequences. When vitamin C was added to tramadol, the distal and proximal convoluted tubules, and the renal glomeruli, improved. When vitamin C was given to the tramadol group, the drug's harmful effects on the kidney were reduced.

"Aging-Related Changes in Rat Kidney and Testis: A Microscopic Approach"

"Aging-Related Changes in Rat Kidney and Testis: A Microscopic Approach"

Histological and ultrastructural changes in rat kidneys in the early period after paraoxone poisoning

Introduction. Toxic nephropathies are not limited to a single morphological type of kidney tissue damage. The widespread distribution of organophosphorus compounds (OPs) in the modern world makes it necessary to study the morphological manifestations and delayed effects of OPs on various organs and tissues of the human and animal body. Material and methods. The article presents the results of a study of changes in the kidneys of rats at the ultrastructural level in the early stages after a single injection of paraoxon at doses of LD50 and LD84. Results. It has been shown that after the introduction of paraoxon, the epithelial cells of the convoluted tubules are initially damaged, and a week after the poisoning, changes are recorded in the renal corpuscle, manifested in an increase in the thickness of the glomerular basement membrane. Limitations. Morphological changes in the renal tissues were analyzed in a single poisoning at doses of LD50 and LD84. Conclusion. The changes detected in the renal corpuscles indicate the feasibility of further studies on the effect of FOS on the nature, sequence and mechanism of nephrotoxic effects of FOS in models of acute and chronic intoxication.

The effect of modulators of hydrogen sulfide metabolism on morphological changes in kidneys of rats with high-calorie diet-induced obesity

Annotation. Obesity is one of the factors in the development of chronic kidney disease. Hydrogen sulfide (H2S) plays an important role in regulating the functional state of the kidneys, and its endogenous production is disrupted in obesity. The search for effective and safe correctors of H2S metabolism in the kidneys in obesity is relevant. The aim of the study was to establish the effect of potential modulators of H2S metabolism on biochemical and morphological changes in the kidneys of rats with high-calorie-diet-induced obesity (DIO). The experiments were performed on 60 white male laboratory rats in accordance with the principles of bioethics (Strasbourg, 1986; Kyiv, 2001). DIO was modeled using a high-calorie high-fat diet (39.5% fat per calorie). Metabolic correction was performed with H2S metabolism modulators (zinc sulfate, sodium thiosulfate, lipoic acid, taurine). Control rats received a standard diet (10.5% fat per calorie). Somatometric parameters, H2S level, morphological changes of kidney tissue were determined. Statistical processing was performed in the package IBM Statistics SPSS 26, differences were assessed in the Kruskel-Wallis test at a significance level of p&lt;0.05. It was found that the development of DIO was accompanied by a decrease in the concentration of H2S in the kidneys (1.9 times, p&lt;0.001), characteristic morphological changes in renal tissue with damage of the glomerular and tubular apparatus, severe inflammatory reaction of the parenchyma, endothelial damage and vascular structure. All metabolic correctors increased the level of H2S in the kidneys and inhibited the progression of nephropathy under the conditions of DIO. Zinc sulfate and lipoic acid were the most effective in preserving the structural elements of the renal parenchyma, while sodium thiosulfate and taurine were less effective.

Evaluation of the effect of vitamin D on acyclovir-induced renal injury in adult male albino rat

Acyclovir (ACV) is a commonly used antiviral drug useful in the treatment of several viral infections. However, its clinical application is limited by severe nephrotoxicity. Vitamin D (VD) regulates cell growth, cell differentiation, and the immune system and prevents neoplastic transformation. Recent studies reported that vitamin D and its analogs have protective effects in renal dis-eases. The present study aimed to examine the protective effect of vitamin D on acyclovir-induced nephrotoxicity in rats. 40 adult male albino rats were divided into 4 groups. Group I (control group). Group ІІ animals received vita-min D intraperitoneally at a dose of 0.5 μg/kg per day for 10 days. Group ІІI animals received acyclovir intraperitoneally at a dose of 150 mg/kg per day for 10 days. Group ІV animals received vitamin D (0.5 μg/kg/day) and acyclo-vir (150 mg/kg/day) for 10 days. At the end of the experiment, the kidneys were removed, weighed, and sampled for histopathological, immunohisto-chemical, and biochemical studies. Vitamin D decreased elevated serum cre-atinine, blood urea nitrogen, renal malondialdehyde (MDA) and immunoex-pression of the proapoptotic protein (Bax) induced by ACV. It increased re-duced glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dis-mutase (SOD), and immunoexpression of the antiapoptotic protein (Bcl2). It also ameliorated the morphological changes induced by ACV. ACV has ne-phrotoxic effects as indicated by biochemical, histological, and immunohisto-chemical alterations. VD was found to have protective effects against ACV-induced nephrotoxicity through the improvement of kidney function, and histopathological changes in rat kidney.

Cardamomin protects from diabetes-induced kidney damage through modulating PI3K/AKT and JAK/STAT signaling pathways in rats

BackgroundDiabetic nephropathy is one of the common complications of diabetes mellitus, which seriously affects the life quality and health of patients. In this study, we aimed to investigate the function of cardamonin (CAD) in diabetes-induced kidney damage in rats. MethodsThe normal rat kidney tubular epithelial cells (NRK-52E) were pre-treated with different doses of CAD and then stimulated with methylglyoxal (MGO). Streptozotocin (STZ) induced diabetes rat model were received different doses of CAD treatment. MTT, EdU, Transwell, and flow cytometry was used to detect cell viability, proliferation, migration, and apoptosis. Western blot analysis was used to detect the expression of apoptosis related proteins, advanced glycation end-products (AGEs), receptor for AGEs (RAGE), epithelial mesenchymal transition (EMT) related proteins, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway related proteins, and janus kinas/signal transducer and activator of transcription 3 (JAK/STAT3) related proteins. ELISA assay was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). The levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were detected using commercial kit. Hematoxylin and eosin staining was used to assess pathological changes in rat kidney. ResultsCompared with control group, MGO reduced cell viability and proliferation, enhanced migration and apoptosis of NRK-52E cells, while CAD inhibited these effects induced by MGO in NRK-52E cells. Moreover, CAD increased Bcl-2 expression and decreased the expression of Bax and cleaved caspase-3 in MGO-treated NRK-52E cells. Compared with control group, MGO increased the AGEs formation, the expression of RAGE and p-p65, the levels of TNF-α, IL-6, IL-1β, MDA in NRK-52E cells and reduced the levels of GSH and SOD, while treatment of CAD dose-dependently prevented these results. In addition, CAD attenuated MGO-induced EMT of MGO-treated NRK-52E cells. Mechanically, we identified that CAD repressed PI3K/AKT and JAK/STAT3 signaling in NRK-52E cells. Importantly, the kidney injury of diabetes rats was attenuated by CAD. Besides, STZ-induced inflammatory response, oxidative stress, and phosphorylation levels of PI3K, AKT, JAK2, and STAT3 were reduced by CAD in the rats. ConclusionCAD protects from diabetes-induced kidney damage through modulating PI3K/AKT and JAK/STAT signaling pathways in rats.

TGF-β/Smad signaling pathway plays a crucial role in patulin-induced pro-fibrotic changes in rat kidney via modulation of slug and snail expression

Patulin (PAT) is a mycotoxin that contaminates a variety of food and foodstuffs. Earlier in vitro and in vivo findings have indicated that kidney is one of the target organs for PAT-induced toxicity. However, no study has evaluated the chronic effects of PAT exposure at environmentally relevant doses or elucidated the detailed mechanism(s) involved. Here, using in vitro and in vivo experimental approaches, we delineated the mechanism/s involved in pro-fibrotic changes in the kidney after low-dose chronic exposure to PAT. We found that non-toxic concentrations (50 nM and 100 nM) of PAT to normal rat kidney cells (NRK52E) caused a higher generation of reactive oxygen species (ROS) (mainly hydroxyl (•OH), peroxynitrite (ONOO−), and hypochlorite radical (ClO−). PAT exposure caused the activation of mitogen-activated protein kinases (MAPKs) and its downstream c-Jun/Fos signaling pathways. Moreover, our chromatin immunoprecipitation (ChIP) analysis suggested that c-Jun/Fos binds to the promoter region of Transforming growth factor beta (TGF-β1) and possibly induces its expression. Results showed that PAT-induced TGF-β1 further activates the TGF-β1/smad signaling pathways. Higher activation of slug and snail transcription factors further modulates the regulation of pro-fibrotic molecules. Similarly, in vivo results showed that PAT exposure to rats through gavage at 25 and 100 μg/kg b. wt had higher levels of kidney injury/toxicity markers namely vascular endothelial growth factor (VEGF), kidney Injury Molecule-1 (Kim-1), tissue inhibitor of metalloproteinase-1 (Timp-1), and clusterin (CLU). Additionally, histopathological analysis indicated significant alterations in renal tubules and glomeruli along with collagen deposition in PAT-treated rat kidneys. Overall, our data provide evidence of the involvement of ROS mediated MAPKs and TGF-β1/smad pathways in PAT-induced pro-fibrotic changes in the kidney via modulation of slug and snail expression.

Exosomes from Umbilical Cord-Originated Mesenchymal Stem Cells (MSCs) Prevent and Treat Diabetic Nephropathy in Rats via Modulating the Wingless-Related Integration Site (Wnt)/β-Catenin Signal Transduction Pathway

For the exosomes secreted by umbilical cord-originated mesenchymal stem cells (so-called hucMSC-exo), they can be applied to treat a variety of clinical diseases as a therapeutic strategy. The Wnt/β-catenin signal pathway has received widespread attention for its capability to modulate multiple kinds of diseases including diabetic nephropathy. Our study aimed to assess the therapeutic efficiency of exosomes secreted by hucMSC-exo on the rat model with diabetic nephropathy (DN). Rats were given an intraperitoneal injection of streptozotocin (60 mg/kg) to induce diabetes, while rats in blank group received same amount of buffer. The DN rats were randomized into DN group and treatment group (treated with hucMSC-exo) followed by analysis of total urine protein, creatinine and urea nitrogen in serum, the histopathological changes in rat kidneys and Wnt-4 and β-catenin expression by western blot. In comparison with the rats in DN group, those in hucMSC-exo treatment group exhibited significantly reduced indexes related to urinary and renal function biochemical tests (P &lt; 0.05). HE staining of kidney tissues showed that abnormal degree of renal damage was significantly alleviated after treatment. In addition, exosomes can ameliorate the symptoms of renal damage in DN rats through modulating the Wnt-4/β-catenin signal pathway. It provides an experimental basis for hucMSC-exo as a new treatment method for DN. hucMSC-exo can ameliorate the renal function and the tissue damage in DN rats through impeding Wnt-4/β-catenin signal pathway thereby providing a basis for the prevention and treatment of DN.

Co-administration of hydroalcoholic Viola odorata’s extract and streptozotocin on histopathological and biochemical changes in rat kidney

Co-administration of hydroalcoholic Viola odorata’s extract and streptozotocin on histopathological and biochemical changes in rat kidney

Protective effect of garlic juice on renal function and lipid profile in rats fed with high-fat diet

Background: Hyperlipidemia is one of the most challenging clinical disorders and is known to be a causative factor in a number of related conditions. Garlic has traditionally been used to lower serum lipids in hyperlipidemia patients. The present study evaluates the renoprotective role of garlic against induced changes in rat kidneys as a result of a high-fat diet (HFD). Materials and Methods: Twenty adult male Wistar rats were arranged into 4 groups: Group 1 (control) were fed a normal rat diet; Group 2 were fed an HFD (butter in a dose of 20g/100g food); Group 3 were fed fresh garlic juice (GJ) in their diet (6g/100g food); and Group 4 were fed with butter and GJ in their diet (HFD + GJ). The experimental period was 8 weeks. Serum lipid profiles and renal function tests were carried out and evaluated. Results: The HFD significantly increased body weight, total serum cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), uric acid, creatinine, and blood urea nitrogen (BUN), and decreased total protein and albumin, as compared to the control. In the HFD + GJ group, normal body weight was restored; serum levels of total cholesterol, creatinine, BUN, and albumin were similar to the control, and serum levels of triglyceride, LDL-C, uric acid, and total protein were partially restored to the levels of the control. Conclusions: The incorporation of GJ into an HFD resulted in improved lipid profile and kidney function. Hence, the consumption of GJ may be a useful supplement for renal protection in hyperlipidemic patients.

Ameliorative Role of Diallyl Disulfide Against Glycerol-induced Nephrotoxicity in Rats

ABSTRACTIntroduction:This study investigated the role of diallyl disulfide (DADS) against glycerol-induced nephrotoxicity in rats. Moreover, the role of peroxisome proliferator activated receptor-γ (PPAR-γ) in DADS-mediated renoprotection has been explored.Materials and Methods:Male Wistar albino rats were challenged with glycerol (50% w/v, 8 mL/kg intramuscular) to induce nephrotoxicity. Kidney injury was quantified by measuring serum creatinine, creatinine clearance, urea, potassium, fractional excretion of sodium, and microproteinuria in rats. Renal oxidative stress was measured in terms of thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione levels. Hematoxylin–eosin (H&E) and periodic acid Schiff staining of renal samples was done to show histological changes. Glycerol-induced muscle damage was quantified by assaying creatine kinase (CK) levels in rat serum.Results:Administration of glycerol resulted in muscle damage as reflected by significant rise in CK levels in rats. Glycerol intoxication led kidney damage was reflected by significant change in renal biochemical parameters, renal oxidative stress and histological changes in rat kidneys. Administration of DADS attenuated glycerol-induced renal damage. Notably, pretreatment with bisphenol A diglycidyl ether, a PPAR-γ antagonist, abolished DADS renoprotection in rats.Conclusion:We conclude that DADS affords protection against glycerol-induced renal damage in rats. Moreover, PPAR-γ plays a key role in DADS-mediated renoprotective effect.

Ameliorative role of bosentan, an endothelin receptor antagonist, against sodium arsenite-induced renal dysfunction in rats.

Arsenic exposure is well documented to cause serious health hazards, such as cardiovascular abnormalities, neurotoxicity and nephrotoxicity. In the present study, we intended to explore the role of bosentan, an endothelial receptor antagonist, against sodium arsenite-induced nephrotoxicity and hepatotoxicity in rats. Sodium arsenite (5 mg/kg, oral) was administered for 4 weeks to induce renal dysfunction in rats. Sodium arsenite intoxicated rats were treated with bosentan (50 and 100 mg/kg, oral) for 4 weeks. Arsenic led renal damage was demonstrated by significant increase in serum creatinine, urea, uric acid, potassium, fractional excretion of sodium, microproteinuria and decreased creatinine clearance in rats. Sodium arsenite resulted in marked oxidative stress in rat kidneys as indicated by profound increase in lipid peroxides, and superoxide anion generation alongwith decrease in reduced glutathione levels. Hydroxyproline assay highlighted arsenic-induced renal fibrosis in rats. Hematoxylin-eosin staining indicated glomerular and tubular changes in rat kidneys. Picrosirius red staining highlighted collagen deposition in renal tissues of arsenic treated rats. Immunohistological results demonstrated the reduction of renal eNOS expression in arsenic treated rats. Notably, treatment with bosentan attenuated arsenic-induced renal damage and resisted arsenic-led reduction in renal eNOS expression. In addition, sodium arsenite-induced alteration in hepatic parameters (serum aspartate aminotransferase, alanine transferase, alkaline phosphatase, bilirubin), oxidative stress and histological changes were abrogated by bosentan treatment in rats. Hence, we conclude that bosentan treatment attenuated sodium arsenite-induced oxidative stress, fibrosis and reduction in renal eNOS expression in rat kidneys. Moreover, bosentan abrogated arsenic led hepatic changes in rats.

Ligusticum chuanxiong Effects on Oxidative Stress and Nrf2/HO-1 Signaling Using Nano-Magnetic Beads in Bleomycin-Induced Renal Fibrosis Rats

Ligusticum chuanxiong can relieve the degree of renal fibrosis. However, the specific mechanism of Ligusticum chuanxiong to improve renal fibrosis is not yet clear. A unilateral ureteral obstruction was used to construct a rat renal fibrosis model. The rats were treated with 20 mg/kg and 40 mg/kg of Ligusticum chuanxiong. Four weeks after treatment, blood was collected from the rats, and the rats were sacrificed. Blood urea nitrogen (BUN), serum creatinine (Scr), kidney tissue malondialdehyde (MDA), and superoxide dismutase (SOD) levels were detected. Hematoxylin–eosin staining was used to observe the pathological rat kidney changes. The renal tissue smooth muscle actin (α-SMA) was detected by immunohistochemistry. Nrf2 and HO-1 levels were determined by PCR using nano-magnetic beads. The results showed BUN, Scr, and MDA levels reduced, while SOD levels were elevated in Ligusticum chuanxiong-treated rats, compared to model rats (P &lt; 0.05). These effects were more dramatic in Ligusticum chuanxiong high dose (HD) rats compared to Ligusticum chuanxiong low dose (LD) rats. Additionally, Nrf2 and HO-1 levels were elevated in Ligusticum chuanxiong-treated rats (P &lt; 0.05). These effects were also more dramatic in HD rats compared to LD rats. These findings indicated that Ligusticum chuanxiong early administration can reduce renal fibrosis in rats by stimulating the Nrf2/HO-1 pathway.

Cyclosporine A induces kidney dysfunction by the alteration of molecular mediators involved in slit diaphragm regulation and matrix metalloproteins: the mitigating effect of curcumin

ABSTRACT Background This research aimed at investigating the cyclosporine A intake impact with/without curcumin on podocyte protein gene expressions and matrix metalloproteins (MMPs) changes in rat kidney. Methods Thirty-two Wistar male rats were assigned to the control, sham, cyclosporine A, and cyclosporine A with curcumin groups. Results A significant increase was observed in CD2AP, ACTN4, podocin and also MMP9 and 2, cystatin C levels in the cyclosporine A group following treatment for four weeks, whereas a decrease was found in nephrin gene expression than the control group. In addition, a significant reduction was observed in the cyclosporine A group in glomerular filtration rate (GFR), urine creatinine, and increased plasma creatinine levels than the control group. Using curcumin plus cyclosporine A ameliorated gene expression alterations and increased the reduced amount of GFR, urine urea, and creatinine while reducing the increased plasma cystatine C, urea, and creatinine levels compared with the cyclosporine A group. Conclusion Accordingly, cyclosporine A-induced kidney abnormalities are possibly associated with changes in podocyte intra- and extra-cellular protein gene expression that influence the quality of filtrated fluid via altering the foot process shape and slit diaphragm size. Finally, such impacts are reduced via curcumin as an antioxidant and anti-inflammatory compound.

Stevioside protects against rhabdomyolysis-induced acute kidney injury through PPAR-γ agonism in rats.

We explored the potential role of peroxisome proliferator activated receptor-γ (PPAR-γ) in stevioside-mediated renoprotection using rhabdomyolysis-induced acute kidney injury (AKI) model in rats. Rhabdomyolysis refers to intense skeletal muscle damage, which further causes AKI. Glycerol (50% w/v, 8 ml/kg) was injected intramuscularly in rats to induce rhabdomyolysis. After 24 hr, AKI was demonstrated by quantifying serum creatinine, urea, creatinine clearance, microproteinuria, and electrolytes in rats. Further, oxidative stress was measured by assaying thiobarbituric acid reactive substances, generation of superoxide anion, and reduced glutathione levels. Additionally, serum creatine kinase (CK) level was assayed to determine glycerol-induced muscle damage in rats. Pathological changes in rat kidneys were studied using hematoxylin-eosin and periodic acid Schiff staining. Moreover, the expression of apoptotic markers (Bcl-2, Bax) in rat kidneys was demonstrated by immunohistochemistry. Stevioside (10, 25, and 50 mg/kg) was administered to rats, prior to the induction of AKI. In a separate group, bisphenol A diglycidyl ether (BADGE, 30 mg/kg), a PPAR-γ receptor antagonist was given prior to stevioside administration, which was followed by rhabdomyolysis-induced AKI in rats. The significant alteration in biochemical and histological parameters in rats indicated AKI, which was attenuated by stevioside treatment. Pretreatment with BADGE abrogated stevioside-mediated renoprotection, which is suggestive of the involvement of PPAR-γ in its renoprotective effect. In conclusion, stevioside protects against rhabdomyolysis-induced AKI, which may be attributed to modulation of PPAR-γ expression.

Bendiocarb-induced nephrotoxicity in rats and the protective role of vitamins C and E.

Bendiocarb is a pesticide carbamate which is used to protect agricultural products and animals. In this study, rats were given orally with bendiocarb and also other chemicals via gavage. Male rats were randomly divided into eight groups (n = 6): group 1 served as controls; group 2 received vitamin C (100mg/kg bw); group 3 received vitamin E (100mg/kg bw); group 4 received vitamins C plus E; group 5 received bendiocarb (0.8mg/kg 1/50 LD50); group 6 received both bendiocarb and vitamin C; group 7 received both bendiocarb and vitamin E; and group 8 received both bendiocarb and vitamin C and E via oral gavage. Degenerative changes and biochemical differences in rat kidney were investigated after 4weeks of especially bendiocarb treatment. While biochemical values were normal in the control group, it was observed that CAT, SOD, GPx, and GST values decreased, while MDA, creatine, urea, and uric acid values increased in the pesticide-treated groups. It was also reported that bendiocarb caused cytopathological and histopathological changes in rat kidney. We have shown that the application of vitamins has a therapeutic effect on the evaluated parameters.

In situ metabolomics in nephrotoxicity of aristolochic acids based on air flow-assisted desorption electrospray ionization mass spectrometry imaging

Understanding of the nephrotoxicity induced by drug candidates is vital to drug discovery and development. Herein, an in situ metabolomics method based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was established for direct analysis of metabolites in renal tissue sections. This method was subsequently applied to investigate spatially resolved metabolic profile changes in rat kidney after the administration of aristolochic acid I, a known nephrotoxic drug, aimed to discover metabolites associated with nephrotoxicity. As a result, 38 metabolites related to the arginine–creatinine metabolic pathway, the urea cycle, the serine synthesis pathway, metabolism of lipids, choline, histamine, lysine, and adenosine triphosphate were significantly changed in the group treated with aristolochic acid I. These metabolites exhibited a unique distribution in rat kidney and a good spatial match with histopathological renal lesions. This study provides new insights into the mechanisms underlying aristolochic acids nephrotoxicity and demonstrates that AFADESI-MSI-based in situ metabolomics is a promising technique for investigation of the molecular mechanism of drug toxicity.

Boron, a Trace Mineral, Alleviates Gentamicin-Induced Nephrotoxicity in Rats.

The present study was considered to assess the protective effects of boron (B) on gentamicin-induced oxidative stress, proinflammatory cytokines, and histopathological changes in rat kidneys. Rats were split into eight equal groups which were as follows: control (fed with low-boron diet); gentamicin group (100 mg/kg, i.p.); B5, B10, and B20 (5, 10, and 20 mg/kg B, i.p.) groups; gentamicin (100 mg/kg, i.p.) plus B5, B10, and B20 (5, 10, and 20 mg/kg B, i.p.) groups. B was given to rats 4 days before the gentamicin treatment and B administration was completed on the 14th day. Gentamicin administration was started on the 4th day and finished on the 12th day. Gentamicin increased malondialdehyde levels, while reduced glutathione levels in the blood and kidney. Furthermore, superoxide dismutase and catalase activities of erythrocyte were decreased. Besides, serum and kidney nitric oxide and 8-dihydroxyguanidine levels were increased by gentamicin. Additionally, serum levels and kidney mRNA expressions of TNF-α, NFκB, IL-1β, and IFN-γ were found to be the highest in the gentamicin group. Histopathologically, interstitial hemorrhage and tubular necrosis were detected in the kidneys of the gentamicin group. Nonetheless, B administration reversed gentamicin-induced lipid peroxidation, antioxidant status, and inflammation. In conclusion, B has a preventive effect against gentamicin-induced nephrotoxicity and ameliorates kidney tissues of the rat.

Proteomic changes in rat kidney injured by adenine and the regulation of anemoside B4

Proteomic changes in rat kidney injured by adenine and the regulation of anemoside B4