Cisplatin-induced Nephrotoxicity In Rats Research Articles

Vildagliptin Nephroprotective Effect in Rats Model with Cisplatin-Induced Nephrotoxicity

Objective: To evaluate the nephroprotective effect of vildagliptin against cisplatin-induced nephrotoxicity in rats.
 Methods and Materials: Twenty-eight male rats have been divided into four groups: Control (received distal water), cisplatin treated group (received single dose of cisplatin (7mg/kg) intraperitoneally (IP) on day eight), vildagliptin plus cisplatin treated group (received vildagliptin 10mg/kg/day orally for 14 days, seven days before and seven days after the dose of cisplatin on day eight), and vildagliptin treated group (received the same dose and duration of vildagliptin mentioned previously). At the end, blood samples were collected to evaluate tumor necrotic factor-α (TNF-α), caspase-3, total antioxidant capacity (TAOC), urea, and creatinine. The serum levels of these biomarkers were expressed as mean ± standard error of mean. Additionally, kidneys were fixed in formalin for histopathological examination.
 Result: Vildagliptin treatment significantly reduced the serum levels of TNF-α, caspase-3, urea, and creatinine as well as increased the TAOC level in rats treated with vildagliptin plus cisplatin when compared with cisplatin treated group. Histopathological examination further supported the nephroprotective effect of vildagliptin in rats with cisplatin induced nephrotoxicity. 
 Conclusion: Vildagliptin improved kidney function and reduced cisplatin nephrotoxicity which may highlight the nephroprotective effect of this DPP-4 inhibitor against cisplatin-induced nephrotoxicity.

Effect of human umbilical cord blood-mesenchymal stem cells on cisplatin-induced nephrotoxicity in rats.

Cisplatin-containing regimen is an effective treatment for several malignancies. However, cisplatin is an important cause of nephrotoxicity. So, many trials were performed to transplant stem cells systemically or locally to control cisplatin-induced nephrotoxicity. Stem cell therapeutic effect may be dependent on the regulation of inflammation and oxidant stress. To investigate the effect of human umbilical cord blood-mesenchymal stem cells (hUCB-MSCs) on the histological structure, the oxidant stress, and the inflammatory gene expression in an experimental model of cisplatin-induced nephrotoxicity in rats. The rats were divided into 6 equal groups (each of 10 rats): Group I included normal rats that received no treatment. Group II included healthy rats that received IV hUCB-MSCs. Group III included untreated cisplatin-induced nephrotoxic rats. Group IV included cisplatin-induced nephrotoxic rats that received magnesium (Mg) injections after injury. Group V was injected with hUCB-MSCs after injury. Group VI received both Mg and hUCB-MSCs after injury. In tissue homogenates, reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) activities were measured. Quantitative real-time-polymerase chain reaction (qRT-PCR) was performed to assess iNOS, TLR4, and NF-kB gene expression. Hematoxylin and eosin (H&E) staining was performed to study the histological structure of the kidney. Immunohistochemical staining of iNOS and NF-κB was performed, as well. Disturbed kidney functions, oxidative status, and histological structure were seen in the rats that received cisplatin. Treated groups showed improvements in kidney functions, oxidative status, and histological structure, particularly in the combined treatment group. In the cisplatin-induced nephrotoxicity model, hUCB-MSCs could improve the functional and morphological kidney structure by modulation of oxidative and inflammatory status.

Novel insights into the augmented effect of curcumin and liraglutide in ameliorating cisplatin-induced nephrotoxicity in rats: Effects on oxidative stress, inflammation, apoptosis and pyroptosis via GSK-3β

Cisplatin dose-dependent nephrotoxicity is a major issue limiting its proper use in cancer treatment. Inflammation, redox imbalance, and dysregulated cell death are the most plausible underlying pathomechanics. Curcumin and the glucagon-like peptide-1 receptor agonist, liraglutide, have been investigated in various experimental models for their antioxidant, anti-inflammatory, and cell death modulatory effects. Hence, this work was designed to investigate curcumin and liraglutide nephroprotective effects and how they behave together against cisplatin-induced acute kidney injury (AKI) in an experimental Wistar rat model. The study comprised 61 rats divided randomly into 6 unequal groups: control I and II, cisplatin-induced nephrotoxicity, curcumin-treated, liraglutide-treated, and co-treated groups. Renal index, serum nephrotoxicity markers (Cr, BUN, NGAL), renal glycogen synthase kinase-3 β (GSK-3β), oxidant/antioxidant parameters (MDA, MPO, GSH, NQO1, HO-1), and inflammatory biomolecules (TNF-α, IL-1β) were assayed. Moreover, renal cleaved-caspase3 and the pyroptotic biomolecules (nod-like receptor family pyrin domain containing 3, gasdermin D N-terminal fragment) were immunoassayed. Furthermore, relative renal expression of both nuclear factor erythroid 2-related factor 2 (Nr-F2) and caspase1 was evaluated by qRT-PCR. Histopathological examination of renal tissue was carried out along with detection of Bcl-2 and Bax immunoreactivity. Cisplatin induced acute renal damage, augmented inflammation, dysregulated redox balance and induced apoptosis and pyroptosis. On the other hand, curcumin and liraglutide corrected the dysregulated mechanisms and normalized results to a great extent. Mutual use of curcumin and liraglutide exerted the greatest effect in the co-treatment group. Nr-F2/HO-1 axis and GSK-3β play a master role in their nephroprotective effect. In conclusion, curcumin and liraglutide have an ameliorative effect against cisplatin-induced nephrotoxicity and can be used alone or better in combination owing to their augmented effect launching promising avenues for cancer patients under cisplatin treatment, retarding AKI and enabling them to gain the best protocol effectiveness.

Mitigation of cisplatin-induced nephrotoxicity by chelidonic acid in Wistar rats

IntroductionCisplatin, an anti-cancer drug is used to treat a wide range of solid tumors. Nevertheless, nephrotoxicity is the major adverse effect that restricts its clinical application. The present study focuses on the effect of chelidonic acid in cisplatin-induced nephrotoxicity. MethodsWistar rats were injected with cisplatin (5 mg/kg, intraperitoneally (i.p.), once in a week for 4 weeks) and chelidonic acid (10, 20, and 40 mg/kg, per oral (p.o.) for 4 weeks). Body weight, urine, biochemical, and oxidative stress parameters were performed to evaluate the effect of chelidonic acid in cisplatin-induced nephrotoxicity in rats. Pro-inflammatory cytokines and nuclear factor erythroid 2-related factor 2 (Nrf2) concentrations were determined. Expression of phospho-AMP activated protein kinase (phospho-AMP) and hypoxia-inducible factor 1-alpha (HIF-1α) was studied with western blot. Haematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining were used to study kidney tissues. ResultsRelative kidney weight and urine output were significantly increased in cisplatin-administered rats. Whereas, albumin, and creatinine concentration were decreased, and treatment with chelidonic acid reverses these deleterious effects of cisplatin significantly. Kidney functions were improved by chelidonic acid treatment with a reduction in tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and transforming growth factor-beta (TGF-β1) concentration. The oxidative stress was decreased as compared to the cisplatin group. Furthermore, Nrf2 was significantly increased by chelidonic acid treatment. Chelidonic acid treatment significantly increased the expression of phospho-AMPK and HIF-1α in kidney tissue. Histopathological studies revealed that chelidonic acid reduced kidney damage. ConclusionThe findings showed that chelidonic acid increases phospho-AMPK and HIF-1α in the kidney tissue and significantly lowers the inflammatory cytokines, thus it is an effective molecule for providing protection against cisplatin-induced nephrotoxicity.

The ameliorative effect of Primula vulgaris on cisplatin-induced nephrotoxicity in rats and quantification of its phenolic components using LC-ESI-MS/MS

Cisplatin (CDDP) is an important chemotherapeutic agent, accumulation of which in kidney tissue causes nephrotoxicity and renal failure. The aim of this study was to evaluate, for the first time in the literature, the protective effect of dimethyl sulfoxide (DMSO) extract of Primula vulgaris leaf (PVE) against CDDP-induced nephrotoxicity in rats.The PVE content was characterized using liquid chromatography-mass spectrometry. Nephrotoxicity was induced with a single dose of CDDP (7.5 mg/kg). Thirty female Wistar-Albino rats were divided into five groups (control, DMSO, CDDP (7.5 mg/kg), CDDP + PVE (25 mg/kg), and CDDP + PVE (50 mg/kg)). Biochemical and histopathological analyses were then performed.Rutin, gallic acid, p-coumaric acid and protocatechuic acid were identified as major components of PVE. Total antioxidant status and glutathione (GSH) values increased significantly in the serum samples from the treatment group compared to the CDDP group, while blood urea nitrogen, creatinine, oxidative stress index, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), total oxidant status, and 8-hydroxy-2′-deoxyguanosine (8-OHdG) values decreased significantly. GSH levels increased significantly in the treatment group compared to the CDDP group, while TNF-α, caspase-3, 8-OHdG, MDA levels and damage scores decreased significantly.In conclusion, PVE exhibited strong protective effects through its anti-apoptotic, antioxidant, and anti-inflammatory activities against nephrotoxicity and oxidative damage caused by CDDP in rats.

Ameliorative Effect of Olea europaea Leaf Extract on Cisplatin-Induced Nephrotoxicity in the Rat Model.

Olea europaea leaf extract (OELE) has potential health benefits and protects against cytotoxicity. This study investigated the possible ameliorative effect of OELE on cisplatin-induced nephrotoxicity in rats. Rats were assigned into six groups; two groups received 150 mg/kg or 300 mg/kg of OELE, one group received a single dose of cisplatin (6 mg/kg) IP on the first day of the experiment, two groups received a single dose of cisplatin 150 mg/kg or 300 mg/kg of OELE on the first day then starting from the fifth day for 10 consecutive days, and one group acted as a control. Results and Conclusion. The findings showed that cisplatin-induced nephrotoxicity was evidenced by a significant increase in serum creatinine blood urea nitrogen (BUN) and a significant decrease in estimated creatinine clearance and potassium level, which corresponded with the alterations in the histopathology of the renal tissue. OELE significantly ameliorated the nephrotoxic effects of cisplatin as dose-dependent.

Gallic acid and/or cerium oxide nanoparticles synthesized by gamma-irradiation protect cisplatin-induced nephrotoxicity via modulating oxidative stress, inflammation and apoptosis

Cisplatin is one of the most significant anticancer. However, its use is associated with numerous toxicities especially nephrotoxicity. The main aim of this work was to examine the protective effect of Gallic acid (GA) and/or cerium oxide nanoparticles (CONPs) synthesized by gamma-irradiation on cisplatin-induced nephrotoxicity in rats. To do that, 48 adult male albino rats were separated into eight groups and received GA (100 mg/kg orally) and/or CONPs (15 mg/kg i. p.) for 10 days before injection with a single dose of cisplatin (7.5 mg/kg i. p.). The findings showed that cisplatin treatment impaired kidney functioning as shown by elevated serum levels of urea and creatinine. Additionally, the oxidative stress indicators (MDA and NO), levels of NF-kB, pro-inflammatory cytokines (IL1-and TNF-) and pro-apoptotic proteins (BAX and caspase-3) were raised after cisplatin injection, while levels of intrinsic anti-oxidants (CAT, SOD, and GSH) and anti-apoptotic protein (Bcl-2) were reduced. Moreover, renal toxicity was confirmed by alteration in normal histological architecture of the kidneys. On the other hand, pretreatment with CONPs and/or GA ameliorated cisplatin-induced nephrotoxicity as evidenced by improvement of renal function parameters and levels of oxidative stress, inflammatory and apoptotic markers in renal tissue along with the renal histopathological changes. This study clarifies how GA and CONPs protect against cisplatin-induced nephrotoxicity and demonstrates any potential synergism between them. Therefore, they can be considered as promising nephroprotective agents during chemotherapy.

Augmented nephroprotective effect of liraglutide and rabeprazole via inhibition of OCT2 transporter in cisplatin-induced nephrotoxicity in rats

AimsCisplatin, a widely used anticancer treatment, has a marked nephrotoxic effect. This nephrotoxic effect is linked to the triggering of oxidative stress, inflammation, activation of mitogen-activated protein kinase (MAPK) pathway as well as apoptosis. The purpose of the present research was to examine the possible ameliorative effect of liraglutide and/or rabeprazole on cisplatin-induced nephrotoxicity in rats and to underline the potential molecular pathways involved. Main methodsRats were divided into five groups: Control, cisplatin, liraglutide (200 μg/kg/day, i.p), rabeprazole (10 mg/kg/day, orally) and liraglutide + rabeprazole combination groups. All treatments were given for 7 days. Cisplatin was given as a single dose (7 mg/kg, i.p) at day 4 to induce nephrotoxicity in all groups except the control group. Key findingsTreatment with liraglutide and/or rabeprazole prior to cisplatin maintained the function and morphology of kidney via decreasing cisplatin renal uptake by significant inhibition of OCT2. Besides, they showed a significant increase in GLP-1 receptor expression. Liraglutide and/or rabeprazole significantly attenuated the levels of TNF-α. ICAM, NF-κB, and downregulated MAPK pathway proteins such as JNK, and ERK1/2. Moreover, they maintained oxidant antioxidant balance by decreasing MDA level and increasing GSH level and CAT activity. Additionally, liraglutide and/or rabeprazole exhibited antiapoptotic effect evidenced by the decreased caspase-3 level and Bax expression and the increased Bcl-2 expression. SignificanceThe current study showed that both liraglutide and rabeprazole exerted a nephroprotective effect against cisplatin-induced renal toxicity in rats. Interestingly, co-treatment with both drugs showed an augmented effect.

Stepwise solid phase extraction integrated with chemical derivatization for all-in-one injection LC-MS/MS analysis of metabolome and lipidome

The metabolome and lipidome are critical components in illustrating biological processes and pathological mechanisms. Generally, two or more independent methods are required to analyze the two compound panels due to their distinct chemical properties and polarity differences. Here, a novel strategy integrating stepwise solid-phase extraction (SPE) and dansyl chemical derivatization was proposed for all-in-one injection LC-MS/MS analysis of serum metabolome and lipidome. In this workflow, a stepwise elution procedure was firstly optimized to separate the metabolome and lipidome fractions using an Ostro plate. Dansyl chemical derivatization was then applied to label amine/phenol, carboxyl, and carbonyl-containing sub-metabolomes. Our results demonstrated that the dansyl labeling could significantly improve chromatographic separation, enhance the MS response, and overcome the matrix effect of co-eluting lipids. Ultimately, an all-in-one injection LC-MS/MS method measuring 256 lipids (covering 20 subclasses) and 212 metabolites (including amino acids, bile acids, fatty acids, acylcarnitines, indole derivatives, ketones and aldehydes, nucleic acid metabolism, polyamines, etc.) was established. This method was applied to investigate the metabolic changes in cisplatin-induced nephrotoxicity in rats and the results were compared with previous untargeted metabolomics. The presented strategy could predominantly improve the analytical coverage and throughput and can be of great use in discovering reliable potential biomarkers in various applications.

Antioxidant Properties of Protein Extracted from the Brown Seaweed (Sargassum ilicifolium) against Cisplatin-induced Nephrotoxicity in Rats

Antioxidant Properties of Protein Extracted from the Brown Seaweed (Sargassum ilicifolium) against Cisplatin-induced Nephrotoxicity in Rats

Nephroprotective Effect of Methanolic Extract of Solanum nigrum (Mako) and its Fractions on Cisplatin-induced Nephrotoxicity in Albino Rats

Background: Renal failure is an emerging problem worldwide and it is defined as the presence of renal parenchymal damage. Its manifestations are abnormal albumin excretion or decreased kidney function. Solanum nigrum L. (Mako), ‘Black Nightshade’, belongs to the family Solanaceae known in Unani medicine for its nephroprotective activity, especially in renal disease, as the berries are used to treat many renal ailments including renal failure. Aim: The aim of this study was to evaluate the nephroprotective activity of the berries of Mako on cisplatin-induced nephrotoxicity in rats. Methods: Wistar rats were divided into 7 groups of six animals in each. Group I served as the control, group II the toxicant group (cisplatin only), group III included the methanolic extract of Mako, group IV petrol soluble fraction of ME, group V chloroform soluble fraction of ME, group VI water soluble fraction of ME, and group VII the water soluble fraction of ME. All groups except for control group received a single dose of cisplatin 7 mg/kg injection on the 4th day, and test drugs were co-administered from day 1 to day 7. On the 8th day, samples were collected for the analysis of blood urea nitrogen (BUN), serum creatinine and for histopathological examination of renal tissues. Results: Results were analyzed using the one-way analysis of variance followed by Dunnett’s post hoc test. It was revealed that the ME of Mako and its fractions significantly reduced the rise in BUN and serum creatinine levels caused by cisplatin. The histopathological analysis also showed the protective nature of Mako in the nephrotoxic modules. Conclusion: Hence, the biochemical parameters and histopathological results affirmed the nephroprotective effect of the berries of the Mako against cisplatin-induced renal damage.

Cytoprotective potentialities of carvacrol and its nanoemulsion against cisplatin-induced nephrotoxicity in rats: development of nano-encasulation form

Cisplatin (Cisp) is a widely distributed chemotherapeutic drug for cancers. Nephrotoxicity is one of the most common side effects of the use of this drug. Carvacrol (CV) is a common natural compound in essential oils and extracts of medicinal plants with potent in vivo and in vitro bioactivities. The work was extended to achieve the target of investigation of the protective potentialities of CV and its nanoemulsion as a cytoprotective drug against Cisp-induced nephrotoxicity in albino rats. CV-nanoemulsion was prepared by a hydrophilic surfactant polysorbate 80 (Tween 80) and deionized water. The TEM image of the particle distribution prepared nanoemulsion is mainly spherical in shape with particle size varying between 14 and 30 nm. Additionally, the Cisp administration caused the increasing of the levels of urea and creatinine in the blood and serum. These increasing of urea and creatinine levels caused consequently the turbulence of the oxidative stress as well as the rising of hs-CRP, IL-6, and TNF-α levels in the serum. Also, histopathological changes of the kidney tissue were observed. These changes back to normal by treatment with CV-nanoemulsion. Expression levels of nephrotoxicity-related genes including LGALS3, VEGF, and CAV1 in kidney tissue using qRT-PCR were measured. The results revealed that the expression of LGALS3, VEGF and CAV1 genes was highly significantly increased in only Cisp treated group when compared with other treated groups. While, these genes expressions were significantly decreased in Cisp + CV treated group when compared with Cisp treated rats (P < 0.001). In addition, there were no significant differences between Cisp + nano-CV treated group and both negative control and nanoemulsion alone groups but it was not significant. In addition, the Western blot of protein analysis results showed that the LGALS3 and CAV1 are highly expressed only in Cisp + CV treated group compared with other groups. There was no significant difference between Cisp + nano-CV treated animals and negative control for both mRNA and protein expression. Based on these results, CV was combined with calcium alginate; a more stable capsule is formed, allowing for the formation of a double wall in the microcapsule. These results supported the therapeutic effect of CV and its nano-emulsion as cytoprotective agents against Cisp nephrotoxicity.

Detam 1 black soybean against cisplatin-induced acute ren failure on rat model via antioxidant, antiinflammatory and antiapoptosis potential

Background and aimCis-Diamminedichloroplatinum (II) (Cisplatin) is one of the most synthetic anticancer drug but have several adverse effects and one of them is acute ren failure. Cisplatin can induce nephrotoxicity occur via the toxic generation of reactive oxygen species (ROS). Black soybean (Glycine max L. Merr.) has been reported contain high levels of phenolics and anthocyanins that has antioxidant activity. This study aims to determine the effect of ethanol extract of black soybean (EEBS) against cisplatin-induced nephrotoxicity in rats. Experimental procedureCisplatin-induced nephrotoxicity rats treated with EEBS and the blood samples taken on days 0, 9, and 18. The effects of EEBS was evaluated by determining Interferon-γ (IFN-γ), Caspase-3 (Casp-3), and Interleukin-1β (IL-1β) expression using immunohistochemistry (IHC), blood urea nitrogen (BUN), Uric Acid (UA) content and catalase (CAT) content in the blood plasma with colorimetric assay kit. Results and conclusionBased on the results, EEBS treatment had successfully reduced pro-inflammatory cytokines IL-1β and IFN-γ, and improved physiological condition by lowering BUN and UA content while increasing CAT activity. No significant effect was found in Casp-3 expression. EEBS has potential to improve acute renal failure condition through inflammatory suppression and renal function improvement.

Effect of Saxagliptin on Cisplatin-Induced Nephrotoxicity in Rats

Effect of Saxagliptin on Cisplatin-Induced Nephrotoxicity in Rats

The nephroprotective effects of Daucus carota and Eclipta prostrata against cisplatin-induced nephrotoxicity in rats

ABSTRACT The overuse of cisplatin (>50 mg/m2) is limited to nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. The objective of this study was to investigate the nephroprotective effects of Daucus carota and Eclipta prostrata extracts on cisplatin-induced nephrotoxicity in Wistar albino rats. The study involved male Wistar albino rats of 8 weeks weighing 220–270 g. A single injection of 5 mg/kg was injected into the rats for nephrotoxicity. Rats were divided into four groups based on dose conentrations. Blood and urine samples of rats were collected on the 0, 7th, 14th, and 21st days for nephrological analysis. The results showed that Cis + DC/Cis + EP (600 mg/kg) significantly (p < 0.001) increased the body weight and reduced the kidney weight of cisplatin-induced nephrotoxicity in rats (p < 0.001) as compared to Cis group. The results showed that 600 mg/kg administration of Cis + DC/Cis +EP successfully (p < 0.005) improved the urine and plasmin creatinine, Na, and K level compared to the Cis group. Histopathological results confirmed that Cis + EP/Cis + DC effectively improved the renal abnormalities. It is concluded that the co-administration of Cis + EP extract showed exceptional nephroprotective effects at a dose rate of 600 mg/kg.

The effects of apelin-13 against cisplatin-induced nephrotoxicity in rats

Acute kidney injury (AKI) is observed in nearly 60% of patients undergoing cisplatin (CP) therapy. The aim of this study was to reveal the potential effects of apelin-13 (AP-13) in the prevention of CP-induced renal toxicity, together with its antioxidant and anti-inflammatory effect mechanisms. Four experimental groups were established. Group 1, the control group, received 0.9% saline solution alone intraperitoneally (IP). Group 2, the CP group, received CP IP at 5 mg/kg once weekly for four weeks for induction of nephrotoxicity. In Group 3, the CP + Apelin-13 (AP-13) group, AP-13 was prepared at 20 nmol kg/d in sterile pyrogen-free saline before injection every day for four weeks and administered IP. CP was administered IP at 5 mg/kg once weekly for four weeks for induction of nephrotoxicity. In Group 4, the AP-13 group, AP-13 was prepared at 20 nmol kg/d in sterile pyrogen-free 0.9% saline before injection every day for four weeks and administered IP. Thiobarbituric acid reactive substances (TBARS), thiol (-SH), interleukin-1 beta, cleaved caspase-3, 8-hydroxy 2-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-κβ/p65) levels were then measured. Increased oxidative stress, inflammation, and apoptosis as a result of CP application activated the cascade. However, AP-13 administration reduced the oxidative stress increased by CIS with the determined antioxidant effect and reduced the damage by increasing total -SH levels. 8-OHdG and NF-κβ/p65, which were up-regulated by triggering oxidative stress and inflammation, were down-regulated through the antioxidant and anti-inflammatory effects of AP-13.

Assessment of gentamicin and cisplatin-induced kidney damage mediated via necrotic and apoptosis genes in albino rats

BackgroundGentamicin (GM) is a low-cost, low-resistance antibiotic commonly used to treat gram-negative bacterial diseases. Cisplatin (Csp) is a platinum-derived anti-neoplastic agent. This experiment aimed to identify the early signs of gentamicin and cisplatin-induced nephrotoxicity in rats. Thirty Wistar rats were divided into three groups of 10: a control group, which received no treatment; a gentamicin group administered by a dose of (100 mg/kg, IP) for 7 consecutive days, and a cisplatin group was administered intraperitoneal in a dose of (1.5 mg/kg body weight) repeated twice a week for 3 weeks.ResultsBoth experimental groups exhibited increased levels of creatinine, urea, and uric acid, with the cisplatin-treated group showing higher levels than the gentamicin group. Experimental groups also exhibited significantly increased Malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GSH-Px) with more pronounced effects in the cisplatin-treated group. Further, both experimental groups exhibited significant up-regulation of Tumor Necrosis Factor α (TNF-α), caspase-3, and Bax and down regulation of Bcl-2.ConclusionThese findings confirm the use of necrotic, apoptotic genes as early biomarkers in the detection of tubular kidney damage. Further, cisplatin was shown to have a greater nephrotoxic effect than gentamicin; therefore, its use should be constrained accordingly when co-administered with gentamicin.

Betaine downregulates microRNA 34a expression via a p53-dependent manner in cisplatin-induced nephrotoxicity in rats.

Cisplatin-induced nephrotoxicity limits its wide application as a chemotherapeutic drug. Betaine is a natural trimethylglycine compound involved in several biological reactions. In this study, the protective effect of betaine against cisplatin-induced nephrotoxicity through modulating the expression of microRNA 34a (miRNA 34a), p53, apoptosis, and inflammation was investigated. Adult Wistar rats were divided into normal group (received vehicle); betaine group (received 250 mg betaine/kg BW/day via oral gavage from Day 1 to Day 25); cisplatin group (received a single intraperitoneal dose of cisplatin at 5 mg/kg BW on Day 21) and betaine + cisplatin group (received the same doses of betaine and cisplatin). The results demonstrated that the cisplatin group exhibited severe kidney tissue damage and an increase in blood creatinine and urea levels. Furthermore, the cisplatin group showed a significant upregulation of miRNA 34a and higher levels of phospho-p53, caspase 3, cytochrome c, NFk B, and IL-1β compared to the normal group. Remarkably, the betaine + cisplatin group showed significantly decreased blood creatinine and urea concentrations, decreased levels of miRNA 34a, phospho-p53, caspase 3, cytochrome c, NFk B, and IL-1β as well as improved kidney tissue integrity compared to the cisplatin group. In conclusion, cisplatin-induced nephrotoxicity in rats was associated with upregulation of miRNA 34a expression, apoptosis, and inflammation in p53-dependent manner. These effects were reversed by betaine administration that ultimately improved the kidney function and tissue integrity.

Abrogation of cisplatin-induced nephrotoxicity in rats and HEK-293 cell lines by formononetin: in vivo and in vitro study

Abrogation of cisplatin-induced nephrotoxicity in rats and HEK-293 cell lines by formononetin: in vivo and in vitro study

Nephroprotective Effects of Zataria multiflora Boiss. Hydroalcoholic Extract, Carvacrol, and Thymol on Kidney Toxicity Induced by Cisplatin in Rats.

Background Cisplatin (Cis) is an anticancer drug; however, it has dose-dependent renal toxicity. The current study aims to investigate the protective effects of Zataria multiflora Boiss. hydroalcoholic extract (Z.M.B), carvacrol, and thymol on cisplatin-induced nephrotoxicity in rats. Materials and Methods Forty-two Wistar male rats were randomly allocated into six groups (n = 7). Group I received normal saline; group II received Cis (7 mg/kg. ip); group III received the Z.M.B extract only (500 mg/kg/d, po); group IV received Z.M.B extract (500 mg/kg/d, po) + Cis; group V received carvacrol (50 mg/kg/d, po) + Cis; and group VI received thymol (50 mg/kg/d, po) + Cis. The levels of biochemical markers, oxidative stress parameters, and histopathological staining were determined in serum and renal tissues. Also, the chemical compositions (carvacrol and thymol) of the Z.M.B extract were assayed by HPLC analysis. Result The results revealed that Z.M.B extract, carvacrol, and thymol markedly decreased the renal index as compared with the Cis-only group. Also, carvacrol and thymol significantly reduced the blood urea nitrogen level as compared with the Cis-only group. Furthermore, Z.M.B extract, carvacrol, and thymol significantly attenuated the Cis-induced increase in malondialdehyde and nitric oxide metabolite. Additionally, histopathological examination showed that Z.M.B extract, carvacrol, and thymol markedly ameliorated Cis-induced renal tubular necrosis. Conclusion The results showed renoprotective effects of Z.M.B extract, carvacrol, and thymol in Cis-induced nephrotoxicity in rats. Therefore, Z.M.B extract can be considered as a potential candidate for the protection of nephrotoxicity induced by Cis.