Cisplatin-induced Kidney Damage Research Articles

Taxifolin attenuates cisplatin-induced kidney damage in rats via suppressing p53 and iNOS

Cisplatin (CP) is a platinum-based anticancer drug used to treat many different solid tumors. Although cisplatin has strong anticancer properties, its clinical use is limited due to side effects such as ototoxicity, neurotoxicity, myelosuppression and nephrotoxicity. Taxifolin (Tax) is reported to exhibit various possess effects such as anti-inflammatory, antioxidant, antimicrobial, antiviral and anticancer. In this study, we aimed to investigate the possible effects of Tax on CP-induced nephrotoxicity. This study consisted of Control (C), Taxifolin (Tax), Cisplatin (CP) and Cisplatin + Taxifolin (CP + Tax) groups, and there were 6 rats in each group. CP was administered to rats intraperitoneally (i.p.) in a single dose of 7 mg/kg, and Tax was administered orally at a dose of 50 mg/kg for 7 consecutive days. Histopathologically, significant changes such as tubular epithelial degeneration and necrosis, tubular dilatation, inflammatory cell infiltrates, hyaline cast, and glomerular atrophy were detected in the CP group. It was seen that the CP+Tax group significantly reduced histopathological changes (p

Unraveling the Nephroprotective Potential of Papaverine against Cisplatin Toxicity through Mitigating Oxidative Stress and Inflammation: Insights from In Silico, In Vitro, and In Vivo Investigations.

Cisplatin is a potent compound in anti-tumor chemotherapy; however, its clinical utility is hampered by dose-limiting nephrotoxicity. This study investigated whether papaverine could mitigate cisplatin-induced kidney damage while preserving its chemotherapeutic efficacy. Integrative bioinformatics analysis predicted papaverine modulation of the mechanistic pathways related to cisplatin renal toxicity; notably, mitogen-activated protein kinase 1 (MAPK1) signaling. We validated protective effects in normal kidney cells without interfering with cisplatin cytotoxicity on a cancer cell line. Concurrent in vivo administration of papaverine alongside cisplatin in rats prevented elevations in nephrotoxicity markers, including serum creatinine, blood urea nitrogen, and renal oxidative stress markers (malondialdehyde, inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines), as tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6). Papaverine also reduced apoptosis markers such as Bcl2 and Bcl-2-associated X protein (Bax) and kidney injury molecule-1 (KIM-1), and histological damage. In addition, it upregulates antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) while boosting anti-inflammatory signaling interleukin-10 (IL-10). These effects were underlined by the ability of Papaverine to downregulate MAPK-1 expression. Overall, these findings show papaverine could protect against cisplatin kidney damage without reducing its cytotoxic activity. Further research would allow the transition of these results to clinical practice.

Candesartan protects from cisplatin-induced kidney damage via the GDF-15 pathway.

The aim of this study was to explore the protective effect of candesartan against cisplatin-induced kidney damage, with a specific focus on the growth differentiation factor 15 (GDF-15) pathway. 24 adult female Wistar rats, with a weight range of 200-210 grams, were enrolled in the study. Eight rats were included as a normal control group and did not receive any medication. 16 rats were administered cisplatin at a dosage of 2.5 mg/kg/day twice a week for 4 weeks (total dose 20 mg/kg). Then, they were randomly divided into two groups and treated with 1 ml/kg/day tap water or 8 mg/kg/day candesartan via oral gavage daily for 4 weeks. At the end of the treatment period, animals were sacrificed, and their kidneys were assessed histologically. In addition, plasma malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), creatinine, and GDF-15 levels were assessed. Treatment with candesartan resulted in a significant rise in serum GDF-15 levels and a significant reduction in levels of serum MDA, TNF-α, IL-6, and creatinine compared to the cisplatin and saline group. Candesartan treatment effectively protected the kidney injury, and histopathological examinations of the kidneys confirmed these results. This study demonstrates that candesartan alleviates cisplatin-induced renal toxicity by further increasing GDF-15, downregulating inflammatory markers, and reducing oxidative stress.

Evaluation of the healing and protective properties of adipose-derived mesenchymal stem cells from cisplatin-induced liver and kidney damage.

The occurrence of nephrotoxicity and hepatotoxicity as a result of cisplatin administration is a major concern in clinical practice. This study examined the potential protective effects of administering mesenchymal stem cells (MSCs) on the renal and hepatic damage caused by cisplatin. Moreover, the study investigated the potential protective effects of administering Adipose-Derived Mesenchymal Stem Cells (ADMSC) to counteract the harmful effects of cisplatin-induced kidney and liver damage. Male Sprague-Dawley rats were divided into three groups: normal control, cisplatin + saline, and cisplatin + ADMSC. Cisplatin was administered to induce toxicity, and ADMSC was administered intravenously as a potential therapeutic intervention. Biochemical parameters and histopathological changes were assessed in the kidney and liver tissues. Statistical analyses were performed using a one-way ANOVA. Cisplatin increased malondialdehyde (MDA), tumor necrosis factor alfa (TNF-alfa), IL-6, alanine transaminase (ALT), creatinine, Galectin-3, Tissue growth factor beta 1 (TGF-beta 1), compared to the normal control group. Cisplatin-MSC reduced these levels. Histopathology showed that cisplatin caused kidney tubular epithelial necrosis, luminal necrotic debris, tubular dilatation, interstitial inflammation, liver sinusoidal and central vein dilatation, congestion, necrosis, and cytoplasmic vacuolization. ADMSC administration significantly reduced histopathological changes. These findings highlight the potential therapeutic benefits of mesenchymal stem cell (MSC) administration in mitigating cisplatin-induced nephrotoxicity and hepatotoxicity. MSC treatment demonstrated protective effects by reducing oxidative stress, inflammatory markers, and histopathological alterations. Further investigations are warranted to elucidate the precise mechanisms underlying these protective effects and evaluate their clinical implications for managing cisplatin-induced organ damage.

Novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives as potential anticancer agents

Selenocompounds protect against damage to healthy cells and induce the death of tumor cells by apoptosis; for this reason, they are attractive compounds for cancer research. In the present study, two series of novel phenoxy-((phenylethynyl) selanyl) propan-2-ol derivatives were synthesized, and their anti-proliferation activities were evaluated. Of the 23 compounds synthesized, most showed potent anti-proliferative activity against human cancer cell lines. Specifically, compounds 3h, 3g, and 3h-2, which had a 2- or 4-position halogen substituent on 1-((phenylethynyl)selanyl)-3-phenoxypropan-2-ol, exhibited the best anti-proliferative activity against tumor cells. Flow cytometry demonstrated that 3h, 3g, and 3h-2 induced G2/M phase arrest and apoptosis in A549 cells. Cellular studies demonstrated that the induction of apoptosis by 3h correlated with changes in the expression of cell cycle-related proteins and apoptosis-related proteins. Xenograft tumor experiments in nude mice revealed that compound 3h has antitumor effects in vivo and no evident toxic effects in nude mice. In addition, compound 3h alleviated cisplatin-induced liver and kidney damage. These findings uncover the applicability of compound 3h as a novel lead compound for cancer treatment.

Preparation, characterization and protective effect of chitosan - Tripolyphosphate encapsulated dihydromyricetin nanoparticles on acute kidney injury caused by cisplatin

Dihydromyricetin (DMY) is a natural dihydroflavonol compound known for its diverse pharmacological benefits. However, its limited stability and bioavailability posed significant challenges for further applications. To address these issues, in this study, an ion crosslinking method was utilized to prepare chitosan nanoparticles that were loaded with DMY. The synthesized chitosan nanoparticles (CS-DMY-NPs) were spherical in shape with particle size and ζ potential of 198.7 nm and 45.05 mV, respectively. Furthermore, in vitro release experiments demonstrated that CS-DMY-NPs had sustained release and protective effects in simulated gastric and intestinal fluids. CS-DMY-NPs exhibited better antioxidant activity by ABTS and DPPH radical scavenging activity than free DMY. In vivo study showed that CS-DMY-NPs alleviated cisplatin-induced kidney damage by inhibiting oxidative stress and proinflammatory cytokines, and had better activity compared to DMY (free). Immunofluorescence data showed that CS-DMY-NPs activated the Nrf2 signaling pathways in a dose-dependent manner to combat cisplatin-induced kidney damage. Our results demonstrate that CS-TPP has good compatibility with DMY, and CS-DMY-NPs exhibited better protective effects against cisplatin-induced acute kidney injury (AKI) than free DMY.

The Role of EGCG on the Expression of p38 MAPK, IL-6 and TNF-α Biomarker Proteins in the Cisplatin Induced Kidney Damage in Rats

The Role of EGCG on the Expression of p38 MAPK, IL-6 and TNF-α Biomarker Proteins in the Cisplatin Induced Kidney Damage in Rats

Nephroprotective Effect of Diosmin against Cisplatin-Induced Kidney Damage by Modulating IL-1β, IL-6, TNFα and Renal Oxidative Damage.

Cisplatin (CP) is a platinum compound of the alkylating agent class that is used for the treatment of various types of cancer. However, CP treatments in cancer patients are accountable for nephrotoxicity, as it is a major adverse effect. Hence, this research study was proposed to investigate the nephroprotective effect of diosmin, a flavonoid glycoside of hesperidin derivatives against cisplatin-induced kidney damage. Wistar rats received a single intraperitoneal (i.p) injection of CP (7.5 mg/kg, i.p) to induce nephrotoxicity. The administration of CP significantly (p < 0.001) increased the markers of kidney function test (creatinine, blood urea nitrogen, and uric acid) and demonstrated histopathological changes in the kidney of the CP-treated nephrotoxic group. In addition, the CP-treated nephrotoxic group demonstrated a significant (p < 0.001) increase in lipid peroxidation (LPO) levels and depleted activities of reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT).However, diosmin (100 and 200 mg/kg) treatments significantly reduced the elevated levels of kidney function test parameters and restored structural changes in the kidney (p < 0.001). The administration of diosmin (100 and 200 mg/kg) significantly (p < 0.001) reduced LPO levels, increased GSH content and showed improvements in the activities of GPx, GR, SOD and CAT. The markers of inflammatory cytokines such as IL-1β, IL-6 and TNFα significantly (p < 0.001) increased in the CP-treated nephrotoxic group, whereas diosmin (100 and 200 mg/kg) treatments significantly (p < 0.001) reduced the elevated levels of these cytokines. The findings of this research demonstrate the nephroprotective effect of diosmin against CP-induced kidney damage. Therefore, we conclude that diosmin may be used as a supplement in the management of nephrotoxicity associated with CP treatments in cancer patients.

Toll-like Receptor Agonist CBLB502 Protects Against Cisplatin-induced Liver and Kidney Damage in Mice.

CBLB502, a Toll-like receptor-5 agonist derived from Salmonella flagellin, exerts protective roles against irradiation and chemical drugs in mammalian tissues and stimulates tissue regeneration. This study aimed to investigate whether CBLB502 can protect against liver and kidney damage induced by the chemotherapeutic drug cisplatin (CDDP) and the underlying mechanism of the protective effect. Mice were pretreated with CBLB502 [0.2 mg/kg, intraperitoneal (i.p.) injection] 0.5 h prior to administration of CDDP (20 mg/kg, i.p. injection), and analyses of the liver and kidney indices, blood biochemistry, and histopathology were performed. Pretreatment with CBLB502 alleviated CDDP-induced liver and kidney damage. RNA sequencing and bioinformatic analysis indicated that CDDP induced a similar damage-promoting gene regulation pattern in the liver and kidney. CBLB502 protected against liver and kidney damage only after CDDP treatment primarily via different pathways. However, some CBLB502-regulated genes were common between the liver and kidney, including those involved in blood coagulation, fibrinolysis, hemostasis, apoptotic regulation, NF-kappaB signaling, and response to lipopolysaccharide, suggesting a general protective effect by CBLB502. Our data provide insights into the protective mechanism of CBLB502 against CDDP-induced tissue damage in the liver and kidney and might provide a basis for future studies on functional genes and regulatory mechanisms that mediate protection against chemoradiotherapy-induced damage.

Eucalyptol alleviates cisplatin-induced kidney damage in rats

This study was aimed to explore the therapeutic effect of eucalyptol on cisplatin induced kidney damage in Wistar albino rats. The animals were divided into four groups: sham (S), eucalyptol (E), cisplatin (C), and cisplatin + eucalyptol (CE) randomly, six animals in each group. Groups C and CE were received cisplatin (12 mg/kg, a single dose, intraperitoneally (i.p.)). Groups E and CE were treated with eucalyptol (100 mg/kg, for seven days, orally). The blood samples and kidney tissues were collected following sacrification and analyzed histopathologically and biochemically. Histopathological results revealed tubular degeneration and necrosis, inflammatory cell infiltration, tubular lumen dilatation, enlargement of bowman’s space and hyaline cast were significantly irregular in the group C than group S. However, eucalyptol treatment (CE) modulated the alterations in the group C. Serum levels of blood urea nitrogen (BUN) and creatinine (CRE) were considerably higher in the group C compared to the other groups. There was no significant difference among the other groups statistically (except group C) in terms of BUN and CRE values. Eucalyptol treatment (at 100 mg/kg, for seven days) decreased the cisplatin induced increase in serum BUN and CRE levels and restored the reduced Vit C level and CAT activity of kidneys caused by cisplatin. Thus, eucalyptol’s antioxidative, nephroprotective, and curative effects indicated the potential for future drug development.

Ameliorating Effect of Propofol on Cisplatin-Induced Liver and Kidney Damage in Rats

Ameliorating Effect of Propofol on Cisplatin-Induced Liver and Kidney Damage in Rats

Loss of sphingosine kinase 2 protects against cisplatin-induced kidney injury.

Cisplatin is an established chemotherapeutic drug for treatment of solid-organ cancers and is the primary drug used in the treatment of head and neck cancer; however, cisplatin-induced nephrotoxicity largely limits its clinical use. Inhibition of sphingosine kinase 2 (SphK2) has been demonstrated to alleviate various kidney diseases. Therefore, we hypothesized that inhibition of SphK2 could also protect against cisplatin-induced nephrotoxicity. Results from the present study showed that the SphK2 inhibitor ABC294640 or knockdown of SphK2 by siRNA blocked the cisplatin-induced increase of cellular injury markers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and cleaved caspase-3) by Western blot analysis in HK-2 cells, a human renal tubular cell line. In addition, SphK2 inhibition blocked cisplatin-induced activation of NF-κB by Western blot analysis and immunostaining analysis. Furthermore, SphK2 inhibition suppressed cisplatin-induced increases of proinflammatory markers (NLR family pyrin domain containing 3, interleukin-1β, and interleukin-6). Genetic deletion of the SphK2 gene in mice further confirmed that inhibition of SphK2 protected against cisplatin-induced kidney damage in vivo. Compared with wild-type mice, SphK2 knockout mice exhibited less renal dysfunction and reduced promotion of kidney injury markers, inflammatory factors, tubular morphology damage, and fibrotic staining. At the same time, the SphK2 inhibitor ABC294640 failed to interfere with the activity of cisplatin or radiation in two cell culture models of head and neck cancer. It is concluded that inhibition of Sphk2 protects against cisplatin-induced kidney injury. SphK2 may be used as a potential therapeutic target for the prevention or treatment of cisplatin-induced kidney injury.NEW & NOTEWORTHY The present study provides new findings that sphingosine kinase 2 (SphK2) is highly expressed in renal tubules, cisplatin treatment increases the expression of SphK2 in proximal tubular cells and kidneys, and inhibition of SphK2 alleviates cisplatin-induced kidney injury by suppressing the activation of NF-κB, production of inflammatory factors, and apoptosis. SphK2 may serve as a potential therapeutic target for the prevention or treatment of cisplatin-induced nephrotoxicity.

Sulindac acetohydrazide derivative attenuates against cisplatin induced organ damage by modulation of antioxidant and inflammatory signaling pathways

This study aimed to explore the mechanisms of action of a sulindac acetohydrazide derivative, N'-(4-dimethylaminobenzylidene)-2-1-(4-(methylsulfinyl) benzylidene)-5-fluoro-2-methyl-1H-inden-3-yl) acetohydrazide, against anticancer drug cisplatin induced organ damage. Using a rodent model, various markers of organ function and signaling pathways were examined and validated by molecular docking studies. The study involves five groups of animals: control, DMSO, CDDP, CDDP + DMFM, and DMFM. Biochemical enzyme activity, histopathology, tissue antioxidant, and oxidative stress markers were examined. RT-PCR and western blot analyses were conducted for the expression of inducible cyclooxygenase enzyme (COX-2), nuclear factor kappa beta (NF-κB), p65, IL-1, TNF-α, and inducible nitric oxide synthase (iNOS). Flow cytometry analysis of CD4 + TNF-α, CD4 + COX-2, and CD4 + STAT-3 cells in whole blood was performed. Structural and dynamic behavior of DMFM upon binding with receptor molecule molecular docking and dynamic simulations were performed using bioinformatics tools and software. Treatment with DMFM reversed cisplatin-induced malondialdehyde (MDA) and nitric oxide (NO) induction, whereas the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD) in the kidney, heart, liver, and brain tissues were increased. DMFM administration normalized plasma levels of biochemical enzymes. We observed a marked decline in CD4 + STAT3, TNF-α, and COX2 cell populations in whole blood after treatment with DMFM. DMFM downregulated the expression factors related to inflammation at the mRNA and protein levels, i.e., IL-1, TNF-α, iNOS, NF-κB, STAT-3, and COX-2. Dynamic simulations and in silico docking data supports the experimental findings. Our experimental and in silico results illustrated that DMFM may affect protective action against cisplatin-induced brain, heart, liver, and kidney damage via reduction of inflammation and ROS.

Enhanced anticancer potency with reduced nephrotoxicity of newly synthesized platin-based complexes compared with cisplatin

As a platinum-containing anticancer drug, cisplatin is the keystone for treating many malignancies. Nephrotoxicity is the main dose-limiting toxicity, and several hydration therapies and supplementary strategies are utilized to reduce cisplatin-induced kidney damage, so the discovery and development of effective and safe antitumor drugs are still on the path of human health. Herein, a new four-coordinated Pt complex [Pt(TSC)Cl] using N(4)-phenyl-2-formylpyridine thiosemicarbazone (HTSC) was synthesized and characterized by single-crystal X-ray diffraction, 1HNMR, FT-IR, LC/MS and CHN elemental analysis. The Pt(TSC)Cl complex revealed antiproliferative activity against A549, MCF-7 and Caco-2 cell lines with a low micromolar IC50 (200–1.75 µM). Specifically, the Pt(TSC)Cl complex displayed more selectivity in Caco-2 cells (IC50 = 2.3 µM) than cisplatin (IC50 = 107 µM) after 48 h of treatment. Moreover, compared with cisplatin, a known nephrotoxic drug, the Pt(TSC)Cl complex exhibited lower nephrotoxicity against Hek293 normal cells. We also found that the Pt(TSC)Cl complex can effectively prevent cancer cell propagation in sub-G1 and S phases and induce apoptosis (more than 90%). Real time PCR and western analysis demonstrated that the expression pattern of apoptotic genes and proteins is according to the intrinsic apoptosis pathway through the Bax/Bcl-2-Casp9-Casp3/Casp7 axis. Collectively, our findings indicated that the Pt(TSC)Cl complex triggers apoptosis in Caco-2 cell lines, while low nephrotoxicity was shown and may be considered a useful anticancer drug candidate for colorectal cancers for further optimization and growth.

MicroRNA-486-5p is implicated in the cisplatin-induced apoptosis and acute inflammation response of renal tubular epithelial cells by targeting HAT1.

The proinflammatory property of cisplatin is potentially destructive andcontributes to the pathogenesis of acute kidney injury (AKI). The role and upstream regulatory mechanism of histone acetyltransferase 1 (HAT1) in acute kidney inflammation are still unknown. We performed RNA sequencing to filter differentially expressed microRNAs (miRNAs) in the kidney tissue of mice with AKI induced by cisplatin and ischemia-reperfusion. Here, we found that miR-486-5p was upregulated and that the expression of HAT1 was reduced in AKI mouse models and injured human renal proximal tubular epithelial cell (HK-2) model induced by cisplatin. miR-486-5p is implicated in cisplatin-induced kidney damage in vivo. Bioinformatics analysis predicted a potential binding site between miR-486-5p and HAT1. The Luciferase reporter assay and Western blot confirmed that miR-486-5p directly targeted the 3'-untranslated region of HAT1 mRNA and inhibited its expression in the cytoplasm of HK-2 cells. In the in vitro study, inhibiting miR-486-5p reduced apoptosis, and the expression of proinflammatory mediators was induced by cisplatin in HK-2 cells. Simultaneously, the downregulation of miR-486-5p inhibited the activation of the toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB). We further found that HAT1 could inhibit apoptosis and the activation of cisplatin on the TLR4/NF-κB pathway and that the upregulation of miR-486-5p reversed this effect. Therefore, the upregulation of miR-486-5p targeting HAT1 promoted the cisplatin-induced apoptosis and acute inflammation response of renal tubular epithelial cells by activating the TLR4/NF-κB pathway, providing a new basis to highlight the potential intervention of regulating the miR-486-5p/HAT1 axis.

Amelioration of Cisplatin-Induced Kidney and Liver Damage in Rabbits by Fresh Carrot (Daucus carota L) Juice.

Amelioration of Cisplatin-Induced Kidney and Liver Damage in Rabbits by Fresh Carrot (Daucus carota L) Juice.

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.

Evaluation of Renoprotective Effects of Our Locally Grown Green Coffee Beans against Cisplatin-Induced Nephrotoxicity in Swiss Albino Mice.

Introduction Nephrotoxicity is the most common and severe side effect of cisplatin. Cisplatin causes nephrotoxicity through free radical production and debilitating cellular antioxidant capacity. Coffee is a commonly consumed drink and its ingredients have antioxidant roles that could bring benefits to patients affected by nephrotoxicity. Thus, the present study aimed to investigate the renoprotective effects of our locally grown green coffee beans against cisplatin-induced nephrotoxicity in Swiss albino mice. Methods The posttest only control group design was employed on a total of thirty male Swiss albino mice. The mice were divided into five groups: group I (normal control group) received distilled water; group II (negative control group) received distilled water; and groups III–V (treatment groups) received 100, 200, and 300 mg/kg BW/day of green coffee bean extract for 14 days, respectively. Nephrotoxicity was induced in groups II–V by a single intraperitoneal injection of cisplatin (7.5 mg/kg). All mice were sacrificed after 14 days and blood was drawn to evaluate kidney function tests (serum creatinine and serum blood urea nitrogen). Besides, body weight, relative kidney weight, and kidney histopathology were investigated. Result Our results showed that treatment of cisplatin alone (group II mice) significantly increased serum creatinine, serum blood urea nitrogen, relative kidney weight, and pathological damage to the kidney with a decrease in final body weight. However, low-dose green coffee beans (group III), medium-dose green coffee beans (group IV), and high-dose green coffee beans (group V) mice showed a significant dose-dependent decrease in serum creatinine, serum blood urea nitrogen, and relative kidney weight. Furthermore, the dose-dependent treatment with green coffee bean extract prevented the decrease in body weight gain and pathological damage to the kidney in mice. Conclusion Our locally grown green coffee beans brought a dose-dependent ameliorative effect and a promising preventive approach against cisplatin-induced kidney damage in mice.

R. vesicarius L. exerts nephroprotective effect against cisplatin-induced oxidative stress

BackgroundCisplatin is an outstanding anticancer drug, but its use has been decreased remarkably due to sever nephrotoxicity. R. vesicarius L. is a leafy vegetable that is evident with anti-angeogenic, anti-inflammatory, anti-proliferative, hepatoprotective, and nephroprotective potential. Therefore, this study was designed to inspect its methanol extract (RVE) for possible nephroprotective effect.MethodsPrimarily, in vitro antioxidant activity of RVE was confirmed based on 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging aptitude. Thereafter, Swiss Albino male mice were treated with cisplatin (2.5 mg/kg) for 5 successive days to induce nephrotoxicity. Recovery from nephrotoxicity was scrutinized by treating the animals with RVE (25, 50, and 100 mg/kg) intraperitoneally (i.p.) for the next 5 consecutive days. After completion of treatment, mice were sacrificed and kidneys were collected. Part of it was homogenized in sodium phosphate buffer for evaluating malondialdehyde (MDA) level, another part was used to evaluate gene (NQO1, p53, and Bcl-2) expression. Moreover, the hydrogen peroxide (H2O2) neutralizing capacity of RVE was evaluated in HK-2 cells in vitro. Finally, bioactive phytochemicals in RVE were determined using gas chromatography–mass spectrometry (GC-MS).ResultsRVE showed in vitro antioxidant activity in a dose-dependent fashion with 37.39 ± 1.89 μg/mL IC50 value. Treatment with RVE remarkably (p < 0.05) decreased MDA content in kidney tissue. Besides, the expression of NQO, p53, and Bcl-2 genes was significantly (p < 0.05) mitigated in a dose-dependent manner due to the administration of RVE. RVE significantly (p < 0.05) reversed the H2O2 level in HK-2 cells to almost normal. From GC-MS, ten compounds including three known antioxidants “4H-Pyran-4-one, 2, 3-dihydro-3,5-dihydroxy-6-methyl-”, “Hexadecanoic acid”, and “Squalene” were detected. The extract was rich with an alkaloid “13-Docosenamide”.ConclusionOverall, RVE possesses a protective effect against cisplatin-induced kidney damage.

Mechanism Prediction of Astragalus membranaceus against Cisplatin-Induced Kidney Damage by Network Pharmacology and Molecular Docking.

Background Cisplatin is a frequently used and effective chemotherapy drug in clinical practice, but severe side effects limit its use, among which nephrotoxicity is considered the most serious and prolonged damage to the body. Astragalus membranaceus (AM) is a well-known herbal medicine, and modern pharmacological studies have confirmed its antioxidant, immunomodulatory, and antiapoptotic effects. Clinical studies have shown that AM and its active components can attenuate cisplatin-induced kidney damage, but the molecular mechanism has not been fully expounded. Materials and Methods First, the components and targets information of AM were collected from the TCMSP, and the relevant targets of cisplatin-induced kidney damage were accessed from the GeneCards and OMIM databases. Then, the core targets were selected by the Venn diagram and network topology analysis, which was followed by GO and KEGG pathway enrichment analysis. Finally, we construct a component-target-pathway network. Furthermore, molecular docking was carried out to identify the binding activity between active components and key targets. Results A total of 20 active components and 200 targets of AM and 646 targets related to cisplatin-induced kidney damage were obtained. 91 intersection targets were found between AM and cisplatin-induced kidney damage. Then, 16 core targets were identified, such as MAPK1, TNF-α, and p53. Furthermore, GO and KEGG pathway enrichment analysis suggested that MAPK, Toll-like receptor, and PI3K-Akt signaling pathways may be of significance in the treatment of cisplatin-induced kidney damage by AM. Molecular docking indicated that quercetin and kaempferol had high binding affinities with many core targets. Conclusion In summary, the active components, key targets, and signaling pathways of AM in the treatment of cisplatin-induced kidney damage were predicted in this study, which contributed to the development and application of AM.