scholarly journals Effect of zinc supplementation on chronic hepatorenal toxicity following oral exposure to glyphosate-based herbicide (Bushfire®) in rats

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052092534
Author(s):  
Emmanuel Vandi Tizhe ◽  
Najume Dogon-Giginya Ibrahim ◽  
Mohammed Yakasai Fatihu ◽  
Suleiman Folorunsho Ambali ◽  
Ikechukwu Onyebuchi Igbokwe ◽  
...  

Objectives To assess the effects of zinc pretreatment on hepatorenal toxicity following chronic exposure to glyphosate-based herbicides in male rats. Methods Following zinc pretreatment (50 mg/kg and 100 mg/kg), 14.4 to 750 mg/kg of oral glyphosate (Bushfire® herbicide) was administered daily for 36 weeks. Thereafter, serum samples were obtained following jugular venipuncture. Liver and kidney samples were processed for histopathological examination. Results Serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase activity as well as levels of bicarbonate, calcium, creatinine were significantly increased following chronic exposure to Bushfire®. Serum levels of sodium, potassium, chloride, total protein, albumin, globulin and urea were unchanged. Moderate to severe coagulative necrosis of hepatocytes as well as glomerular and renal tubular necrosis were observed in herbicide-treated rats. Zinc pretreatment reduced the elevation of serum enzymes associated with hepatobiliary lesions, abrogated hypercalcemia and metabolic alkalosis, and mitigated serum accumulation of creatinine following Bushfire® exposure, but was ineffective in completely preventing histological lesions. Conclusion Chronic Bushfire® exposure in rats caused hepatorenal toxicity. The effects of exposure on serum parameters were ameliorated by zinc pretreatment, but the histopathological changes associated with toxicity persisted in milder forms in zinc-pretreated animals.

2021 ◽  
pp. 096032712199190
Author(s):  
AA Dar ◽  
A Fehaid ◽  
S Alkhatani ◽  
S Alarifi ◽  
WS Alqahtani ◽  
...  

Methotrexate (MTX) is frequently used drug in treatment of cancer and autoimmune diseases. Unfortunately, MTX has many side effects including the hepato-renal toxicity. In this study, we hypothesized that Luteolin (Lut) exhibits protective effect against the MTX-induced hepato-renal toxicity. In order to investigate our hypothesis, the experiment was designed to examine the effect of exposure of male rats to MTX (20 mg/kg, i.p., at day 9) alone or together with Lut (50 mg/kg, oral for 14 days) compared to the control rats (received saline). The findings demonstrated that MTX treatment induced significant increases in the liver and kidney functions markers in serum samples including Aspartate transaminase (AST), Alanine transaminase (ALT), creatinine, urea and uric acid. MTX also mediated an oxidative stress expressed by elevated malondialdehyde (MDA) level and decreased level of reduced glutathione (GSH), antioxidant enzyme activities, and downregulation of the Nrf2 gene expression as an antioxidant trigger. Moreover, the inflammatory markers (NF-κB, TNF-α, and IL-1β) were significantly elevated upon MTX treatment. In addition, MTX showed an apoptotic response mediated by elevating the pro-apoptotic (Bax) and lowering the anti-apoptotic (Bcl-2) proteins. All of these changes were confirmed by the observed alterations in the histopathological examination of the hepatic and renal tissues. Lut exposure significantly reversed all the MTX-induced changes in the measured parameters suggesting its potential protective role against the MTX-induced toxicity. Finally, our findings concluded the antioxidative, anti-inflammatory and anti-apoptotic effects of Lut as a mechanism of its protective role against the MTX-induced hepato-renal toxicity in rats.


2008 ◽  
Vol 27 (3) ◽  
pp. 223-230 ◽  
Author(s):  
MW Roomi ◽  
T Kalinovsky ◽  
V Ivanov ◽  
M Rath ◽  
A Niedzwiecki

Acetaminophen (APAP) overdose is often fatal, leading to fulminant hepatic and renal tubular necrosis in humans and animals. We studied the effect of a nutrient mixture (NM) containing, among other nutrients, lysine, proline, ascorbic acid, N-acetyl cysteine, and green tea extract, which has previously been demonstrated to exhibit a broad spectrum of therapeutic properties on APAP-induced hepatic and renal damage in ICR (Imprinting Control Region) mice. Seven-week-old male ICR mice were divided into four groups (A–D) of five animals each. Groups A and C mice were fed a regular diet for 2 weeks, while groups B and D mice were supplemented with 0.5% NM (w/w) during that period. Groups A and B received saline i.p., while groups C and D received APAP (600 mg/kg) i.p. All animals were killed 24 h after APAP administration, serum was collected to assess the liver and kidney functions, and the livers and kidneys were excised for histology. Mean serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, BUN (Blood Urea Nitrogen), creatinine, and BUN/creatinine ratios were comparable in groups A and B, increased markedly in group C and significantly lower in group D compared with group C. APAP caused significant centrilobular necrosis and glomerular damage in unsupplemented animals, while NM prevented these alterations. The results indicate that NM has potential to protect against APAP-induced liver and kidney damage.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Abdulsamad Alsalahi ◽  
Mahmood Ameen Abdulla ◽  
Mohammed Al-Mamary ◽  
Mohamed Ibrahim Noordin ◽  
Siddig Ibrahim Abdelwahab ◽  
...  

Hepato- and nephrotoxicity of Khat consumption (Catha edulisForskal) have been evoked. Therefore, this study was conducted to evaluate such possible hepatorenal toxicity in female and male Sprague-Dawley rats (SD rats) focusing primarily on liver and kidney. In addition, female and male rats were investigated separately. Accordingly, forty-eight SD-rats (100–120 g) were distributed randomly into four groups of males and female (n=12). Normal controls (NCs) received distilled water, whereas test groups received 500 mg/kg (low dose (LD)), 1000 mg/kg (medium dose (MD)), or 2000 mg/kg (high dose (HD)) of crude extract ofCatha edulisorally for 4 weeks. Then, physical, biochemical, hematological, and histological parameters were analyzed. Results in Khat-fed rats showed hepatic enlargement, abnormal findings in serum aspartate aminotransferase (AST), and alkaline phosphatase (ALP) of male and female SD-rats and serum albumin (A) and serum creatinine (Cr) of female as compared to controls. In addition, histopathological abnormalities confirmed hepatic and renal toxicities of Khat that were related to heavy Khat consumption. In summary, Khat could be associated with hepatic hypertrophy and hepatotoxicity in male and female SD-rats and nephrotoxicity only in female SD-rats.


2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Kingsley C. Patrick-Iwuanyanwu ◽  
Iniobong A. Charles

The present investigation was aimed to determine the effect of sub-chronic exposure to Solignum<sup>®</sup>, a permethrin-containing wood preservative on biochemical and histological changes in liver and kidneys of male Wistar albino rats. Thirty-two male rats were randomly divided into four groups: control and three treatment concentrations containing 8 rats each. The treatment groups were exposed to Solignum<sup>®</sup> at dose rates of 100, 200 and 400 mg/kg body weight (BW) respectively per day orally for four weeks. Data obtained from the study showed a progressive increase in the body weight of rats in control whereas, rats treated with different concentrations (100, 200 and 400 mg/kg BW) of Solignum<sup>®</sup> decreased significantly (≤0.05) especially at the end of the second and fourth week when compared with control. On the other hand, there was a significant decrease in the relative liver weights of rats treated with 100 and 200 mg/kg BW Solignum<sup>®</sup> while rats treated with 400 mg/kg BW showed a significant increase when compared with control. The relative weight of kidneys in experimental groups increased significantly when compared with control. Biochemical analysis results illustrated that there was a significant increase in marker enzymes namely alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activity at the end of the fourth week. Similarly, total bilirubin, serum urea, creatinine and electrolytes (Na<sup>+</sup>, K<sup>+</sup> and Cl<sup>-</sup>) levels increased in a dose dependent manner in treated rats when compared with untreated control group. Serum total protein decreased significantly in experimental rats when compared with control. However, cholesterol and triglycerides showed no significant difference when compared with control. Histopathological examination of hepatocytes in treated rats was characterized by mild periportal inflammatory cells and cytoplasmic degeneration. Furthermore, histopathological examination of rat kidneys revealed inflammatory cells, congested vessel and interstitial hemorrhage in rats treated with Solignum<sup>®</sup>. Therefore, this present study is aimed to evaluate the hepatotoxic and nephrotoxic potentials associated with sub-chronic exposure to the commercial pesticide Solignum<sup>®</sup>.


2012 ◽  
Vol 60 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Chun-Nam Cha ◽  
Won-Chul Jung ◽  
Hyunju Choi ◽  
Yeo Lee ◽  
Chang-Yeul Yoo ◽  
...  

The present study evaluated the effects of exposure to different doses of sodium chlorate in 10-week-old pigs. Twenty pigs were divided into four equal groups and treated with different doses of sodium chlorate: 0, 125, 250 and 500 mg kg−1body weight per day via the drinking water for 7 consecutive days. The results showed a significant decrease (P < 0.05) in red blood cell and white blood cell counts, packed cell volume, haemoglobin, blood urea nitrogen (P < 0.001) and creatinine levels, and an increase in aspartate aminotransferase and alanine aminotransferase (P < 0.05) activities in swine administered sodium chlorate at a dose of 500 mg kg−1body weight per day. The histopathological study revealed increased numbers of vacuoles in the convoluted tubules, tubular necrosis and degeneration of the renal tubular epithelial cells, depletion of nuclei and lobular necrosis of the liver in all pigs treated with sodium chlorate at 500 mg kg−1body weight per day. Thus, 7-day administration of sodium chlorate at 500 mg kg−1body weight per day to pigs affects the liver and kidney tissues as well as the haematologic and serum biochemical parameters.


Author(s):  
A. V. YADAV ◽  
C. D. UPASANI

Objective: The current study was designed to evaluate the protective effect of standardized hydroalcoholic extract of Plumeria rubra (HAEPR) against cisplatin-induced nephrotoxicity in Wistar rats.  Methods: HAEPR was administered orally at 3 dose levels (100,200,400 mg/kg). Vitamin E (250 mg/kg) was used as a Standard nephroprotective agent. The kidney function test (estimation of serum creatinine, albumin, blood urea nitrogen) oxidative stress study (estimation of superoxide dismutase, malondialdehyde activity) and histological examination of kidneys was conducted. Results: The efficacy of HAEPR was compared with Cisplatin (CP) treated group. Serum creatinine and BUN was significantly (p<0.01) elevated in CP-treated group compared to the control group. HAEPR (100,200 mg/kg) and Vitamin E (250 mg/kg) significantly (p<0.01) decreased the serum creatinine and BUN levels. CP treated group exhibited significant (p<0.01) decrease in albumin when compared to control. Significant (p<0.01) increase in the serum albumin level was found in HAEPR (100,200 mg/kg) and Vitamin E (250 mg/kg) compared to CP group. Significant (p<0.01) decrease in the activity of SOD was observed in the CP group as compared to control. HAEPR (100 and 200 mg/kg) and Vitamin E (250 mg/kg) significantly (p<0.01) increased SOD levels. HAEPR (400 mg/kg) significantly (p<0.05) increased SOD levels. HAEPR (100,200,400 mg/kg) significantly (p<0.01) decreased MDA levels as compared to CP group. Histopathological examination of the kidneys showed that HAEPR markedly ameliorated Cisplatin-induced renal tubular necrosis. An extract was found effective at all doses, although low dose (100 mg/kg) was found to be more effective and comparable with the standard group (Vitamin E 250 mg/kg).  Conclusion: Present investigation revealed that HAEPR resulted in attenuation of Cisplatin-induced renal damage in rats.


2017 ◽  
Vol 34 (3) ◽  
pp. 158-168 ◽  
Author(s):  
Ying Dong ◽  
Fang Li ◽  
Haijun Shen ◽  
Rongzhu Lu ◽  
Siqi Yin ◽  
...  

Dichloroacetonitrile (DCAN), an emerging nitrogenous disinfection by-product, is more genotoxic and cytotoxic than the currently regulated carbonaceous disinfection by-products such as haloacetic acids. Few mechanistic studies have been conducted on the hepatic and renal toxicities of DCAN. This study examined the clinical biochemical, hematological, histopathological, oxidative, and mitochondrial functional alterations to evaluate the systematic toxicity after subacute oral exposure of 11 or 44 mg/kg/day in rats for 28 days. Body and spleen weights were lower, and organ-to-body weight ratios of the liver and kidney were higher in rats administered 44-mg/kg DCAN than in controls. The activities of serum alanine aminotransferase and alkaline phosphatase, and concentrations of blood serum urea nitrogen and retinol-binding protein were increased in rats administered 44-mg/kg DCAN compared with those of controls, thereby indicating hepatic and renal damage in this group. This was confirmed by histopathological alterations, including hepatic sinus dilation, extensive hemorrhage, vacuolar degeneration in the liver and glomerulus hemorrhage, and renal tubular swelling, in DCAN-exposed rats. Exposure to 44-mg/kg DCAN induced hepatic oxidative damage shown by the significant increase in malonaldehyde levels, a poisonous product of lipid peroxidation. Exposure to 44-mg/kg DCAN significantly increased hepatic glutathione content and mitochondrial bioenergy as noted by the elevation of mitochondrial membrane potential and cytochrome c oxidase activity, which might be attributed to compensatory pathophysiologic responses to DCAN-induced hepatic mitochondrial damage.


1995 ◽  
Vol 14 (3) ◽  
pp. 221-230 ◽  

Potassium Chlorate is an inorganic salt that is intended for use in cosmetic ingredients as an oxidizing agent, but there are no current uses reported. Oral administration of Potassium Chlorate with 36C label to rats produced elimination of the label as chloride, chlorate, and chlorite, in descending order of percentage. Potassium Chlorate causes mechanical fragility in erythrocytes and is a catalase inhibitor. In animals dosed orally with Potassium Chlorate, renal tubular necrosis has been seen. Only one mutagenicity study was available, the results of which were negative. A 6-month study in male rats of the tumor promotion potential of Potassium Chlorate caused no effect. Chlorate salts are considered toxic to humans with the lethal ingested dose estimated at 15 to 35 g. Toxic effects of lower doses in humans are seen in the kidneys, gastrointestinal tract, and blood (erythrocytes). Toxic effects in humans appear to be cumulative. The available data were insufficient to support the safety of this ingredient in cosmetic formulations. Additional data are considered necessary to evaluate the safety of this ingredient, including purpose of use and likely concentration of use in cosmetics, 28-day dermal toxicity data, ocular irritation data (if intended for use on or near the eye), two mutagenicity studies (if results are positive, carcinogenicity data are needed), human irritation data as a function of dose, and human sensitization data. It cannot be concluded that this ingredient is safe for use in cosmetic products until the listed safety data have been obtained and evaluated.


Author(s):  
Abeer F. Mostafa ◽  
Mahmoud M. Elalfy ◽  
Ahmed Shata ◽  
Mona G. Elhadidy

AbstractObjectivesUlcerative colitis (UC) is a non-specific intestinal inflammatory disease. Several studies demonstrated that inflammation and oxidative stress play significant role in the pathogenesis of this disease. This study aimed to determine the protective effect and possible mechanism by which stevia affects the course of experimentally induced colitis.MethodsMale rats were received stevia 20, 40, 80 mg/kg/day before induction of colitis by intra-rectal administration of 2 mL of 4% acetic acid, AA. Macroscopic and histopathological examination of the colon were done. Colonic content of catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), myeloperoxidase (MPO) and thiobarbituric acid reactive substances (TBARS) activities and serum levels of interleukin (IL)1- β and tumor necrosis factor (TNF)-α were assessed. Real time-PCR (RT-PCR) was done to determine the expression of NF-κB, Nrf2 and PPARγ genes. Spontaneous contraction and effects of increasing concentrations of acetylcholine and stevia have been studied on the isolated colonic segments.ResultsStevia ameliorated colitis not only histopathologically but also it decreased the level of TNF-α, IL-1β, TBARS, MPO and the expression of NF-κB which were significantly increased in the AA group. The concentration of GSH, SOD, CAT and expression of Nrf2 and PPARγ were significantly increased with stevia. Moreover, stevia showed a relaxant effect on the colonic contractility which was increased in AA group. These all effects of stevia were more prominent with its highest dose.ConclusionOur results explored that, stevia acts protectively against UC by its anti-inflammatory and antioxidant properties which mediated by up-regulation of Nrf2 and PPARγ with downregulation of NF-κB. We suggest that stevia has the potential for treatment of chronic inflammatory diseases, such as UC.


Author(s):  
T. M. Vidhyalakshmi ◽  
S. K. Raval ◽  
P. V. Parikh ◽  
P. V. Patel

Equine theileriosis, an OIE listed disease caused by Theileria equi is an economically important haemoprotozoan disease of horses in tropical and subtropical parts of the world. The aim of the present study was to monitor the biochemical alterations in order to find out the severity of the disease. Standard assay kits were used to study the biochemical parameters of horses positive for theileriosis in comparison with healthy ones. Out of 75 serum samples, 25 samples were collected from horses positive for theileriosis and 50 from healthy horses. The serum levels of GPT (32.00±2.30 U/L), GOT (350.84±27.87 U/L), GGT (20.95±0.92 U/L), LDH (823.74±102.93 U/L), total protein (8.11±0.37 g/dl), globulin (3.84±0.40 g/dl), BUN (46.26±5.27 mg/dl) and creatinine (1.33±0.18 mg/dl) were found to be significantly increased (p less than 0.01) in infected horses compared to the healthy group. Non- significant elevation (p greater than 0.05) in total bilirubin (1.08±0.14 mg/dl), unconjugated bilirubin (0.57±0.11 mg/dl) and glucose (102.57±30.41 mg/dl) as well as non-significant reduction (p>0.05) in conjugated bilirubin (0.42±0.04 mg/dl), albumin (4.26±0.24 g/ dl) and A/G ratio (1.55±0.30) were also observed in infected group. There was no significant alteration (p>0.05) in the level of serum calcium (12.32±0.36 mg/dl) and phosphorus (4.53±0.33 mg/dl), as compared to the healthy group. Significant elevation of GOT, GPT, GGT, BUN and creatinine revealed the involvement of liver and kidney functions in T. equi infected horses.


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