scholarly journals Pioglitazone attenuates kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Branislava Medić ◽  
Marko Stojanović ◽  
Branislav Rovčanin ◽  
Dušan Kekić ◽  
Sanja Radojević Škodrić ◽  
...  

Abstract Gentamicin, belonging to the aminoglycosides, possesses the greatest nephrotoxic effect of all other antibiotics from this group. On the other hand, pioglitazone, which represents peroxisome proliferator-activated receptor γ (PPARγ) agonist recently showed antiinflamatory, antioxidative effects, amelioration of endothelial dysfunction etc. Therefore, the goal of our study was to investigate the effects of pioglitazone on kidney injury in an experimental model of gentamicin-induced nephrotoxicity in rats. These effects were observed by following values of biochemical (serum urea and creatinine) parametars, total histological kidney score, urine level of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) as well as parametars of oxidative stress (malondialdehyde, superoxide dismutase, catalase, total oxidant status, total antioxidant status, oxidative stress index and advanced oxidation protein products). It seems that pioglitazone protects the injured rat kidney in a U-shaped manner. Medium dose of pioglitazone (1 mg/kg, i.p.) was protective regarding biochemical (serum urea and creatinine), total histological score and the values of kidney injury molecule-1 (KIM-1) (P < 0.05 vs. control group, i.e. rats injected with gentamicin only). This finding could be of great importance for the wider use of aminoglycosides, with therapy that would reduce the occurrence of serious adverse effects, such as nephrotoxicity and acute renal failure.

HPB Surgery ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Charalampos Markakis ◽  
Alexandra Tsaroucha ◽  
Apostolos E. Papalois ◽  
Maria Lambropoulou ◽  
Eleftherios Spartalis ◽  
...  

Aim. Acute pancreatitis is an inflammatory intra-abdominal disease, which takes a severe form in 15–20% of patients and can result in high mortality especially when complicated by acute renal failure. The aim of this study is to assess the possible reduction in the extent of acute kidney injury after administration of eugenol in an experimental model of acute pancreatitis. Materials and Methods. 106 male Wistar rats weighing 220–350 g were divided into 3 groups: (1) Sham, with sham surgery; (2) Control, with induction of acute pancreatitis, through ligation of the biliopancreatic duct; and (3) Eugenol, with induction of acute pancreatitis and eugenol administration at a dose of 15 mg/kg. Serum urea and creatinine, histopathological changes, TNF-α, IL-6, and MPO activity in the kidneys were evaluated at predetermined time intervals. Results. The group that was administered eugenol showed milder histopathological changes than the Control group, TNF-α activity was milder in the Eugenol group, and there was no difference in activity for MPO and IL-6. Serum urea and creatinine levels were lower in the Eugenol group than in the Control group. Conclusions. Eugenol administration was protective for the kidneys in an experimental model of acute pancreatitis in rats.


2020 ◽  
Vol 15 (03) ◽  
pp. 05-08
Author(s):  
S. K. Raval ◽  
Monika Patel ◽  
R. J. Modi

The experiment was carried out to study the therapeutic efficacy of aqueous, alcoholic, and biherbal extracts of Vigna unguiculata (VU) and Hordeum vulgare (HV) in ethylene glycol and ammonium chloride-induced urolithiasis in female Wistar rats. Rats were divided into 14 groups, each of 6 rats, except the lithiatic control group, which consisted of 8 rats. Group I and II served as lithiatic and vehicle control, respectively. In group I and III to XIV urolithiasis were induced by administration of 0.75 % (v/v) ethylene glycol and 2% (w/v) ammonium chloride along with drinking water for 28 days. Group II was given 0.5% sodium bicarbonate. After the 28th day, the rats of urolithiatic treatment Groups III to XIV were given aqueous and alcoholic seed extracts of VU and HV @ 200 mg/kg and 300 mg/kg b.wt. orally as either single extract or combination as biherbal extracts (1:1) in 0.5 % sodium bicarbonate for another 35 days using syringe and rat gavage needle. Blood samples were collected twice: on the 28th day of induction of urolithiasis and 63rd day experiment/herbal treatment. Significantly (p less than 0.01) increased levels of calcium, oxalate, phosphate, and decreased levels of magnesium in the kidney homogenate were observed in the calculi induced groups as compared to the vehicle control group on 28th day. However, significantly increased rat Kidney Injury Molecule-1 (KIM-1) was observed in the calculi induced groups as compared to the vehicle control group in serum on the 28th day. Results of kidney homogenate and KIM-1 revealed that aqueous and alcoholic extracts of VU and HV possess good therapeutic efficacy against urolithiasis. The effect of biherbal alcoholic extract of the seeds at higher dose rate was much better in reducing or normalizing the values of most traits by 35 days of treatment, i.e., by 63rd day of the experiment and thus the continuation of treatment for some more days would be expected to restore the normal profile.


2023 ◽  
Vol 83 ◽  
Author(s):  
M. U. Ijaz ◽  
S. A. Majeed ◽  
A. Asharaf ◽  
T. Ali ◽  
K. A. Al-Ghanim ◽  
...  

Abstract Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.


2019 ◽  
Vol 6 (1) ◽  
pp. 41-47
Author(s):  
Hala S. Bash ◽  
Ihsan S. Rabeea

Background: Cisplatin is an anticancer drug used in the management of solid tumors, however, dose-related nephrotoxicity is one of its major problems. Agents having antioxidants, antiinflammatory and/or antiapoptotic activities may thus represent potential therapeutic options to avoid cisplatin-induced nephrotoxicity. Among these agents, coenzyme Q10 has several pharmacological properties including antioxidant, anti-inflammatory and/or anti-apoptotic effects. Objective: The current study aimed to examine whether coenzyme Q10 could attenuate cisplatininduced nephrotoxicity or not. Methods: 24 adult rats were randomly separated into three groups (8 rats per group). The first one was the control group, rats receiving vehicle (olive oil) intraperitoneally. The second group was Cisplatin treated group, rats were receiving 13 mg/kg of Cisplatin intraperitoneally as a single dose. The third group (Cisplatin + Coenzyme Q10), rats were receiving 13 mg/kg as a single intraperitoneal dose of Cisplatin and coenzyme Q10 daily for six consecutive days (10 mg/kg intraperitoneally). Results: Cisplatin caused significant increases in serum creatinine and severe histological lesions. Cisplatin treated group also showed a significant elevation in renal malondialdehyde concentration as a marker of oxidative stress; renal tumor necrosis factor-alpha concentration as a marker of inflammation; and Kidney injury molecule -1 concentration. Coenzyme Q10 significantly attenuated cisplatininduced nephrotoxicity through lowering serum creatinine and improving nephrotoxicity histological scores. Coenzyme Q10 also significantly reduced the renal concentration of MDA, TNF-α and KIM-1 relative to cisplatin treated group. Conclusions: Coenzyme Q10 has a potential nephroprotective effect against cisplatin-induced nephrotoxicity that was demonstrated by biochemical and histopathological analysis.


2016 ◽  
Vol 12 (33) ◽  
pp. 57
Author(s):  
Moses Akiibinu ◽  
Mary Adeyemi ◽  
Toyosi Ogunbiyi ◽  
Mojirade Amusah ◽  
Adeolu Amusan ◽  
...  

Exposures to cement dust have been linked with lung dysfunctions in some occupationally exposed workers. There is a dearth of information on the potentials of the cement particles to induce tumorigenesis, kidney failure and oxidative stress in the exposed workers. This study assessed the effects of cement exposure on macrophage activation, tumor markers, kidney injury molecule-1 and markers of oxidative stress in cement loaders with prolonged exposures. Twenty-nine male workers who had direct exposure to cement dust and gases for a period of 2-30 years in Elephant / Lafarge cement depot Ibadan, Nigeria, were recruited for this study. Another twenty apparently healthy individuals who had no interaction with cement served as controls. Levels of carcino-embryonic antigen (CEA), alpha fetoprotein (AFP), kidney injury molecule-1 (KIM-1), DNA-8-hydroxyguanosine (8-OHdG), neopterin, total plasma peroxide (TPP), total antioxidant potential (TAP), oxidative stress index (OSI), malondialdehyde (MDA) and albumin were determined in all participants using ELISA and spectrophotometry methods respectively. The result shows significantly (p0.05) changes observed in the plasma levels of albumin and AFP when compared with the controls. No significant (p>0.05) correlations could be observed between the levels of 8-OHdG, neopterin, albumin, MDA, CEA, AFP, KIM-1 and OSI in the cement exposed workers. Metabolic disorders including excessive macrophage activation, oxidative DNA damage, kidney diseases and chemically-induced tumors are imminent in cement exposed workers.


Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 754
Author(s):  
Michela Pugliese ◽  
Alessandra Sfacteria ◽  
Gaetano Oliva ◽  
Annastella Falcone ◽  
Manuela Gizzarelli ◽  
...  

This study aimed to investigate the role of oxidative stress parameters (ROMs, OXY, SHp), the Oxidative Stress index (OSi), and High Mobility Group Box-1 protein (HMGB-1) in canine leishmaniosis (CanL). For this study, thirty dogs, naturally infected with Leishmania spp. (Leishmania Group, LEISH) and ten healthy adult dogs (control group, CTR) were included. The diagnosis of CanL was performed by a cytological examination of lymph nodes, real time polymerase chain reaction on biological tissues (lymph nodes and whole blood), and an immunofluorescence antibody test (IFAT) for the detection of anti-Leishmania antibodies associated with clinical signs such as dermatitis, lymphadenopathy, onychogryphosis, weight loss, cachexia, lameness, conjunctivitis, epistaxis, and hepatosplenomegaly. The HMGB-1 and oxidative stress parameters of the LEISH Group were compared with the values recorded in the CTR group (Mann Whitney Test, p < 0.05). Spearman rank correlation was applied to evaluate the correlation between the HMGB-1, oxidative stress biomarkers, hematological and biochemical parameters in the LEISH Group. Results showed statistically significant higher values of SHp in the LEISH Group. Specific correlation between the ROMs and the number of red blood cells, and between HGMB-1 and SHp were recorded. These preliminary data may suggest the potential role of oxidative stress in the pathogenesis of CanL. Further studies are undoubtedly required to evaluate the direct correlation between inflammation parameters with the different stages of CanL. Similarly, further research should investigate the role of ROMs in the onset of anemia.


2018 ◽  
Vol 314 (5) ◽  
pp. F956-F968 ◽  
Author(s):  
David M. Small ◽  
Washington Y. Sanchez ◽  
Sandrine F. Roy ◽  
Christudas Morais ◽  
Heddwen L. Brooks ◽  
...  

Oxidative stress and mitochondrial dysfunction exacerbate acute kidney injury (AKI), but their role in any associated progress to chronic kidney disease (CKD) remains unclear. Antioxidant therapies often benefit AKI, but their benefits in CKD are controversial since clinical and preclinical investigations often conflict. Here we examined the influence of the antioxidant N-acetyl-cysteine (NAC) on oxidative stress and mitochondrial function during AKI (20-min bilateral renal ischemia plus reperfusion/IR) and progression to chronic kidney pathologies in mice. NAC (5% in diet) was given to mice 7 days prior and up to 21 days post-IR (21d-IR). NAC treatment resulted in the following: prevented proximal tubular epithelial cell apoptosis at early IR (40-min postischemia), yet enhanced interstitial cell proliferation at 21d-IR; increased transforming growth factor-β1 expression independent of IR time; and significantly dampened nuclear factor-like 2-initiated cytoprotective signaling at early IR. In the long term, NAC enhanced cellular metabolic impairment demonstrated by increased peroxisome proliferator activator-γ serine-112 phosphorylation at 21d-IR. Intravital multiphoton microscopy revealed increased endogenous fluorescence of nicotinamide adenine dinucleotide (NADH) in cortical tubular epithelial cells during ischemia, and at 21d-IR that was not attenuated with NAC. Fluorescence lifetime imaging microscopy demonstrated persistent metabolic impairment by increased free/bound NADH in the cortex at 21d-IR that was enhanced by NAC. Increased mitochondrial dysfunction in remnant tubular cells was demonstrated at 21d-IR by tetramethylrhodamine methyl ester fluorimetry. In summary, NAC enhanced progression to CKD following AKI not only by dampening endogenous cellular antioxidant responses at time of injury but also by enhancing persistent kidney mitochondrial and metabolic dysfunction.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Xiao-lei Wang ◽  
Tuo Zhang ◽  
Liu-hua Hu ◽  
Shi-qun Sun ◽  
Wei-feng Zhang ◽  
...  

Statins are a promising new strategy to prevent contrast-induced acute kidney injury (CI-AKI). In this study we compared the ameliorative effect of different statins in a rat model of CI-AKI. Sprague-Dawley rats were divided into five groups: control group; CI-AKI group; CI-AKI + rosuvastatin group (10 mg/kg/day); CI-AKI + simvastatin group (80 mg/kg/day); and CI-AKI + atorvastatin group (20 mg/kg/day). CI-AKI was induced by dehydration for 72 hours, followed by furosemide intramuscular injection 20 minutes before low-osmolar contrast media (CM) intravenous injection. Statins were administered by oral gavage once daily for 3 consecutive days before CM injection and once 4 hours after CM injection. Rats were sacrificed 24 hours after CM injection, and renal function, kidney histopathology, nitric oxide (NO) metabolites, and markers of oxidative stress, inflammation, and apoptosis were evaluated. The results showed that atorvastatin and rosuvastatin but not simvastatin ameliorated CM-induced serum creatinine elevation and histopathological alterations. Atorvastatin and rosuvastatin showed similar effectiveness against CM-induced oxidative stress, but simvastatin was less effective. Atorvastatin was most effective against NO system dysfunction and cell apoptosis, whereas rosuvastatin was most effective against inflammation. Our findings indicate that statins exhibit differential effects in preventing CI-AKI when given at equivalent lipid-lowering doses.


2021 ◽  
Author(s):  
Burak Sezgin ◽  
Fatih Pirinççi ◽  
Aysun Camuzcuoğlu ◽  
Eda Adeviye Şahin ◽  
Özcan Erel ◽  
...  

Abstract Purpose: This study aimed to determine the potential clinical use of dynamic thiol disulfide balance in cases with preinvasive lesions of the cervix.Methods: One hundred and sixteen patients with high-grade squamous intraepithelial lesion, one hundred patients with low-grade squamous intraepithelial lesion and one hundred and ten healthy controls were enrolled in the study. A fully automated colorimetric system was used to determine the levels of thiol-disulfide parameters. The ischemia-modified albumin, total oxidant-antioxidant capacity, oxidative stress index of the retrieved cases were further analysed.Results: Native thiol and total thiol levels are significantly lower in the high-grade squamous intraepithelial lesion group according to control group (p:0.004 and p:0.015, respectively). Disulfide level is significantly increased in the high-grade squamous intraepithelial lesion group compared to control group (p:0.004). Oxidative stress index levels in high-grade squamous intraepithelial lesion group were observed as significantly higher according to the control group (p:0.014). Ischemia-modified albumin levels in the high-grade squamous intraepithelial lesion group were observed as significantly higher compared to the control group (p:0.020). Disulfide levels are positively correlated with risk type of Human papillomavirus (r:0.420, p<0.001).Conclusion: The analysis of dynamic thiol disulfide balance revealed considerable oxidative damage in patients with Human papillomavirus -related cervical precursor lesions compared to women with ordinary cytology specimens. Therefore, investigation of thiol disulfide balance with presented method represents a new promising test for early diagnosis and management of women at high risk for cervical cancer.


2018 ◽  
Vol 36 (11) ◽  
pp. 1205-1210
Author(s):  
Didem Arman ◽  
Secil Ercin ◽  
Sevilay Topcuoğlu ◽  
Ayşem Kaya ◽  
Taner Yavuz ◽  
...  

Objective The present study aimed to assess the global oxidant and antioxidant status in infants born to preeclamptic mothers and their correlation with cardiac functions. Study Design We compared 40 infants born to preeclamptic mothers with 40 premature infants born to normotensive mothers. We assessed the relationship between echocardiographic measurements and total antioxidant capacity (TAC) and total oxidant status (TOS) values. Results In the study group, TAC, TOS, and oxidative stress index (OSI) levels were significantly higher in the cord blood (p = 0.03, 0.04, and 0.039, respectively) than in the control group. We did not observe any correlation between echocardiographic measurements and TAC, TOS, and OSI levels in infants born to preeclamptic mothers. Conclusion Compared with the control group, despite higher TAC levels in infants born to preeclamptic mothers, concurrent elevated OSI levels reveal that the oxidant–antioxidant balance is disturbed in favor of oxidants. Furthermore, the findings of this study suggest that echocardiographic parameters are unaffected by the oxidant status.


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