scholarly journals Toxicological effects of thimerosal on rat kidney: a histological and biochemical study

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.

2023 ◽  
Vol 83 ◽  
Author(s):  
N. Ehsan ◽  
M. U. Ijaz ◽  
A. Ashraf ◽  
S. Sarwar ◽  
A. Samad ◽  
...  

Abstract Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Hahn-Ey Lee ◽  
Sun Hee Lee ◽  
Minki Baek ◽  
Hwang Choi ◽  
Kwanjin Park

Background. The study assessed whether measurement of urinary biomarkers of acute kidney injury could be helpful in diagnosing acute pyelonephritis and subsequent scarring. Method. Escherichia coli J96 (0.3 mL inoculum containing 1×109/mL) was directly injected into the renal cortex of 3-week-old female Sprague Dawley rats (n=20), with saline substituted in a control group (n=10). Following the injection, urine was collected 2, 7, 14, 28, and 42 days after injection. Urinary neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and interleukin-18 were quantitatively measured using enzyme-linked immunosorbent assay (ELISA). The levels of the biomarkers were adjusted for creatinine. Time course changes within a group or between the groups were compared. Correlation analysis was performed to understand the relationship between urinary levels and histological scarring. Results. Significantly elevated urinary NGAL was evident at two and seven days after injection, and Kim-1 was elevated at two days after injection. Receiver operating characteristic analyses confirmed the sensitivity of these markers at these times. No urinary marker at acute stage of APN was correlated with the amount of future scarring, negating their predictive value. Conclusion. Urinary NGAL and Kim-1 could be helpful in diagnosing febrile urinary tract infection in children.


2019 ◽  
Vol 20 (4) ◽  
pp. 899 ◽  
Author(s):  
Satoshi Washino ◽  
Keiko Hosohata ◽  
Masashi Oshima ◽  
Tomohisa Okochi ◽  
Tsuzumi Konishi ◽  
...  

Background: Vanin-1 is a novel acute kidney injury (AKI) biomarker that has not been clinically investigated as a biomarker for obstructive nephropathy. This study investigated the diagnostic value of vanin-1 as a biomarker for adult obstructive nephropathy by comparing it to existing AKI biomarkers. Methods: A total of 49 patients, 21 controls, and 28 hydronephrosis (HN) cases were assessed. AKI biomarkers in bladder (BL) urine and renal pelvic (RP) urine in the HN group were compared to each BL marker in the control group. In a subgroup of cases receiving interventions for obstructive nephropathy, the BL values of each biomarker were assessed after the intervention. Results: RP vanin-1 levels were significantly higher while BL vanin-1 levels were marginally higher in the HN group than in the control group. The area under the receiver operating characteristics curve values for RP and BL vanin-1 were 0.9778 and 0.6386, respectively. In multivariate analyses, BL vanin-1 and N-acetyl-β-D-glucosaminidase (NAG), but not kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL), were independent factors for predicting the presence of HN. In cases receiving interventions, vanin-1 decreased significantly from 1 week after the intervention in cases of moderate to severe obstructive nephropathy compared to RP values at baseline. Conclusion: Urinary vanin-1 is a useful biomarker to detect and monitor the clinical course of obstructive nephropathy.


2020 ◽  
Vol 86 (6) ◽  
pp. 741-749
Author(s):  
Eryk Latoch ◽  
Katarzyna Konończuk ◽  
Katarzyna Taranta-Janusz ◽  
Katarzyna Muszyńska-Rosłan ◽  
Edyta Szymczak ◽  
...  

Abstract Introduction Nephrotoxicity is a potential adverse effect of anticancer treatment in childhood. Cytostatics, abdominal radiotherapy, total body irradiation (TBI) and some agents used in supportive care may induce acute kidney injury (AKI) or lead to chronic kidney disease (CKD). The aim of this study was to test the hypothesis whether urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) are increased in acute lymphoblastic leukemia (ALL) survivors. Method The study cohort consisted of 86 patients (42 females) previously treated for ALL. The median time after cessation of treatment was 6.55 (IQR: 1.96–9.93) years and median age at the time of study: 12 (IQR: 6.76–16.00). The control group included 53 healthy peers. Immunoenzymatic ELISA commercial kits were used to measure urine KIM-1 and NGAL levels. Results The median levels of urine uNGAL (p < 0.05), uNGAL/creatinine (cr.) ratio (p < 0.0001) and uKIM-1/creatinine ratio (p < 0.0001) were significantly higher in ALL survivors in comparison with healthy controls. Female patients had significantly higher levels of NGAL and NGAL/cr. than males (mean 8.42 ± 7.1 vs. 4.59 ± 4.5 ng/mL and 86.57 ± 77 vs. 37.7 ± 37 ng/mg, respectively; p < 0.01). Of all the study participants, 11 (13%) presented eGFR below 90 mL/min/1.73 m2. The NGAL/cr. ratio seemed to be the best predictor of decreased eGFR (AUC = 0.65). The cumulative dose of methotrexate and cyclophosphamide did not predict the values of the urine NGAL, NGAL/cr., KIM-1/cr. and eGFR. Five years after the end of treatment, the patients had higher levels of uKIM-1 (1.02 ± 0.8 vs. 0.62 ± 0.6 ng/mL, p < 0.01), uNGAL (7.9 ± 6.7 vs. 4.6 ± 5 ng/mL, p < 0.01) and lower eGFR (114 ± 29 vs. 134 ± 35 mL/min/1.73 m2, p < 0.01) in comparison with ALL survivors with the observation period of less than 5 years. Conclusion We demonstrated that ALL survivors have higher levels of urine NGAL, NGAL/cr. and uKIM-1/cr. ratio as compared to the control group. Further long-term follow-up studies are necessary to assess the significance of the NGAL and KIM-1 and their relationship to kidney damage after anticancer treatment in childhood.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Ming-Chang Kao ◽  
Chih-Yang Chung ◽  
Ya-Ying Chang ◽  
Chih-Kung Lin ◽  
Joen-Rong Sheu ◽  
...  

Limb ischemia/reperfusion (I/R) causes oxidation and inflammation and subsequently induces muscle and kidney injuries. Cepharanthine, a natural plant alkaloid, possesses anti-inflammatory and antioxidative properties. We elucidated the salutary effects of cepharanthine against muscle and kidney injuries following limb I/R. Adult male rats were randomized to receive I/R or I/R plus cepharanthine. I/R was achieved by applying tourniquet high around each thigh for 3 hours followed by reperfusion for 24 hours. Cepharanthine (10 mg/kg, intraperitoneal) was injected immediately before reperfusion. After euthanization, degrees of tissue injury, inflammation, and oxidation were examined. Our data revealed that the I/R group had significant increases in injury biomarker concentrations of muscle (creatine kinase and lactate dehydrogenase) and kidney (creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1). Histological assays revealed moderate muscle and kidney injury characteristics in the I/R group. The I/R group also had significant increases in concentrations of inflammatory molecules (interleukin-6, macrophage inflammatory protein-2, and prostaglandin E2) and reactive nitrogen species (nitric oxide) as well as lipid peroxidation (malondialdehyde). Of note, these effects of limb I/R could be mitigated by cepharanthine. These data confirmed that cepharanthine attenuated muscle and kidney injuries induced by limb I/R. The mechanisms may involve its anti-inflammatory and antioxidative capacities.


2015 ◽  
Vol 309 (12) ◽  
pp. F1009-F1017 ◽  
Author(s):  
Yuping Wang ◽  
Yang Gu ◽  
Susan Loyd ◽  
Xiuyue Jia ◽  
Lynn J. Groome

To investigate kidney injury in preeclampsia, we analyzed 14 biomarkers in urine specimen from 4 groups of pregnant women (normotensive pregnant women and those with pregnancy complicated with chronic hypertension or mild or severe preeclampsia). These biomarkers included 1) podocyte glycoproteins nephrin and podocalyxin, 2) matrix metallopeptidase (MMP)-2 and MMP-9 and their inhibitor tissue inhibitor of metalloproteinase-2, 3) inflammatory molecules and cytokines soluble VCAM-1, TNF-α, soluble TNF receptor receptor-1, IL-6, IL-8, IL-10, and IL-18, and 4) kidney injury biomarkers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Postpartum urine specimens (6–8 wk) from normotensive women and those with severe preeclampsia were also evaluated. We found that, first, urine levels of nephrin, MMP-2, MMP-9, and kidney injury molecule-1 were significantly higher before delivery in severe preeclampsia than normotensive groups. The increased levels were all reduced to levels similar to those of the normotensive control group in postpartum specimens from the severe preeclampsia group. Second, soluble VCAM-1, soluble TNF receptor-1, and neutrophil gelatinase-associated lipocalin levels were significantly increased in the severe preeclampsia group compared with the normotensive control group before delivery, but levels of these molecules were significantly reduced in postpartum specimens in both groups. Third, IL-6 and IL-8 levels were not different between preeclampsia and normotensive groups but significantly increased in pregnancy complicated with chronic hypertension. Finally, tissue inhibitor of metalloproteinase-2 and IL-18 levels were not different among the study groups before delivery but were significantly reduced in postpartum specimens from normotensive controls. Our results indicate that the kidney experiences an increased inflammatory response during pregnancy. Most interestingly, tubular epithelial cell injury may also occur in severe preeclampsia. These biomarkers could be used to assess podocyte or tubular injury and kidney inflammatory responses during pregnancy and to evaluate postpartum kidney injury recovery in pregnancy-complicated disorders.


2018 ◽  
Vol 34 (7) ◽  
pp. 469-480 ◽  
Author(s):  
Ahlem Soussi ◽  
Manel Gargouri ◽  
Abdelfattah El Feki

Lead (Pb) is a toxic metal that induces a wide range of biochemical and physiological effects in humans. Oxidative damage has been proposed as a possible mechanism involved in Pb toxicity. The current study was carried out to evaluate the antioxidant activities of zinc (Zn) supplement against lead acetate–induced kidney injury in rats. In this study, adults male rats were treated for 15 days with Pb (0.344 g/kg body weight (bw)) associated or not with Zn (10 mg/kg bw). Our study showed that supplementation with Zn prevented renal dysfunction as indicated by plasma biomarkers (urea, uric acid, creatinine, lactate dehydrogenase, and alkaline phosphatase levels) and oxidative stress–related parameters (thiobarbituric acid reactive substances, protein carbonyl, advanced oxidation protein product, superoxide dismutase, catalase, glutathione peroxidase, and vitamins (A, E)) in kidney tissue. The corrective effect of Zn on Pb-induced kidney nephrotoxicity recovered normal kidney histology. Overall, this study indicates that Zn alleviated the toxic effects of this heavy metal on renal tissue, suggesting its role as a potential antioxidant and nephroprotective agent.


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.


2020 ◽  
Vol 5 (2) ◽  
pp. 48-53
Author(s):  
Tahmineh Ostovar ◽  
Hosein Rezaei ◽  
Javad Zavar Reza

Introduction: Chronic kidney disease (CKD) is one of the most threatening and important disorders worldwide in both industrial and developing nations. In addition, neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP), and kidney injury molecule-1 (KIM-1) are three factors suggested as diagnostic and prognostic biomarkers in CKDs. Considering the lack of enough efficiency of the creatinine in the prognosis of the CKD, the present study aimed to assess the relationship between these three factors and CKD occurrence and determine if they could be considered valid biomarkers in this regard. Materials and Methods: The present case-control study was designed enrolling 42 patients with confirmed CKD referring to the Imam Khomeini hospital of Kangan. The participants were 42 years old and gender-matched healthy counterparts. Blood samples were obtained, and then NGAL, KIM-1, and L-FABP were determined by the enzyme-linked immunosorbent assay using commercial kits (Bioassay Technology Laboratory). Finally, the serum creatinine was detected by applying Jaffe’s method. Results: Based on the results, significant differences were found in the serum levels of all four factors between CKD patients and the control group. More precisely, the serum levels of NGAL (P < 0.0001, specificity: 87.6%, sensitivity: 79.3%, and the area under the curve, AUC: 0.89), L-FABP (P < 0.0001, specificity: 83.3%, sensitivity: 78.3%, and AUC: 0.86), KIM-1 (P < 0.0001, specificity: 85.7%, sensitivity: 78.6%, and AUC: 0.88), and creatinine (P < 0.0001) were significantly higher in individuals with CKDs in comparison with controls. Eventually, the serum levels of NGAL, L-FABP, and KIM-1 were significantly correlated with each other in both patient and control groups (P < 0.0001). Conclusion: In general, NGAL, L-FABP, KIM-1, and creatinine could be used as independent biomarkers for the diagnosis of CKD. Moreover, the measurement of NGAL, L-FABP, and KIM-1 altogether could be a valid assessment for the diagnosis of CKD.


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.


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