Diethylnitrosamine aggravates cadmium-induced hepatorenal oxidative damage in prepubertal rats

2019 ◽  
Vol 35 (8) ◽  
pp. 537-547 ◽  
Author(s):  
Solomon E Owumi ◽  
Uche J Dim ◽  
Eseroghene S Najophe

The adverse health consequences of environmental, occupational, and dietary exposure to either diethylnitrosamine (DEN) or cadmium (Cd) have been widely investigated. However, because most environmental exposures to xenobiotics do not occur in isolation but in mixtures, the effects of simultaneous exposure to both DEN and Cd on hepatorenal function deserves investigation. The present study investigated the impact of 7 days oral co-exposure to 10 mg/kg body weight (b.w.) of DEN and 5 mg/kg b.w. of Cd on biomarkers of hepatic and renal functions, antioxidant defense systems, and oxidative stress indices in the liver and kidney of prepubertal rats. The results showed that the significant ( p < 0.05) increases in the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, urea, and creatinine following separate administration of DEN and Cd to rats were further increased in the co-exposure group. Moreover, marked decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase as well as glutathione levels following individual administration of DEN and Cd to rats were exacerbated in the co-exposure group. Further, the marked increase in the lipid peroxidation level and the histopathological lesions in the liver and kidney of rats treated with DEN or Cd alone were intensified in the co-exposure group These findings indicate that co-exposure to DEN and Cd elicited more severe hepatic and renal oxidative damage in the rats, thus suggesting a greater risk to humans who are co-exposed to them.

Author(s):  
Solomon E Owumi ◽  
Olabisi F Danso ◽  
Magdalene E Effiong

Exposure to dichloromethane (DCM), a commonly used chlorinated solvent in industrial settings and for the production of many household products, reportedly elicits detrimental effects in animals and humans. The present study investigated the protective role of dietary quercetin on DCM-induced hepatorenal damage in rats. Experimental rats were orally administered with DCM (150 mg/kg) and 30 min later with quercetin at 10, 20 and 40 mg/kg or none for 7 consecutive days. The results indicated that DCM-mediated significant (p<0.05) increases in serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase and alkaline phosphatase activities as well as urea and creatinine levels were dose-dependently normalized to the control values in rats co-treated with quercetin. Further, quercetin co-treatment ameliorated DCM-mediated decrease in the hepatic and renal activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferase as well as glutathione level in the treated rats. Moreover, quercetin co-treatment markedly reduced lipid peroxidation level and protected against histological changes in liver and kidney of the treated rats. Taken together, quercetin abrogated hepatorenal oxidative damage in DCM-treated rats via improvement of antioxidant status and suppression of oxidative damage.


2020 ◽  
Vol 106 (1) ◽  
pp. 174-187
Author(s):  
Rowan S Hardy ◽  
Hannah Botfield ◽  
Keira Markey ◽  
James L Mitchell ◽  
Zerin Alimajstorovic ◽  
...  

Abstract Background The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines prereceptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension (IIH). Methods We conducted a UK multicenter phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017. Serum markers of glucose homeostasis, lipid metabolism, renal and hepatic function, inflammation and androgen profiles were determined and examined in relation to changes in fat and lean mass by dual-energy X-ray absorptiometry. Results Patients receiving AZD4017 showed significant improvements in lipid profiles (decreased cholesterol, increased high-density lipoprotein [HDL] and cholesterol/HDL ratio), markers of hepatic function (decreased alkaline phosphatase and gamma-glutamyl transferase), and increased lean muscle mass (1.8%, P &lt; .001). No changes in body mass index, fat mass, and markers of glucose metabolism or inflammation were observed. Patients receiving AZD4017 demonstrated increased levels of circulating androgens, positively correlated with changes in total lean muscle mass. Conclusions These beneficial metabolic changes represent a reduction in risk factors associated with raised intracranial pressure and represent further beneficial therapeutic outcomes of 11β-HSD1 inhibition by AZD4017 in this overweight IIH cohort. In particular, beneficial changes in lean muscle mass associated with AZD4017 may reflect new applications for this nature of inhibitor in the management of conditions such as sarcopenia.


2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Tarfa Albrahim ◽  
Manal Abdulaziz Binobead

It is common for food to be made more palatable through the use of the flavour enhancer monosodium glutamate, also known as vetsin powder. The purpose of the study described in this paper was to explore how vetsin-induced hepatic toxicity, DNA fragmentation, damage, and oxidative stress modifications could be mitigated with moringa leaf extract (MLE). To that end, 40 male rats were separated into four groups: normal control, positive control or MLE, vetsin, and vetsin combined with MLE. Results indicated that, compared to the control group, the levels of serum alanine aminotransferase (ALT), aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), liver malondialdehyde (MDA), DNA damage, injury, PCNA, and P53 expressions were significantly enhanced by the administration of vetsin (P<0.05). However, the vetsin group had significantly reduced levels of albumin, globulin, total protein, liver glutathione (GSH), superoxide dismutase enzyme (SOD), catalase, and glutathione S-transferase (GST) enzyme activities (P<0.05) by comparison to control. Meanwhile, modifications in liver functions, oxidative stress, DNA damage, liver injury, and PCNA expression were alleviated when vetsin was administered alongside MLE. The authors conclude that vetsin may have many side effects and that MLE can ameliorate biochemical changes, oxidative stress, hepatic injury, PCNA, and P53 alterations induced by vetsin administration.


2021 ◽  
Vol 8 ◽  
Author(s):  
Celeste Ferraris ◽  
Alexandria Turner ◽  
Christopher J. Scarlett ◽  
Martin Veysey ◽  
Mark Lucock ◽  
...  

Single nucleotide polymorphisms (SNPs) in taste receptors influence dietary choices that contribute to health and quality of life. Individual differences in sour taste perception and preference have been linked to heritable genetics, yet the impact of sour taste receptor SNPs on sour taste is under-researched, and studies on sour taste SNP associations to diet and health are lacking. Therefore, this study explored the relationships between the sour taste SNP KCNJ2-rs236514 and estimated macronutrient, vitamin and mineral intakes, and markers of metabolic health. Associations were explored in 523 participants aged 65 years and older with data analysed using standard least squares and nominal logistic regression modelling with post hoc student's t-tests and Tukey's HSD. Associations were found between the presence of the KCNJ2-rs236514 variant allele (A) and lower intakes of energy, total fat, monounsaturated fat and saturated fat. The lower fat intakes were significant in female carriers of the variant allele (A), along with lower water intake. Lower retinol, riboflavin, folate, calcium and sodium intakes were found in the KCNJ2-A allele carriers. In females, the variant allele was associated with lower sodium intake before and after Bonferroni adjustment. Higher body mass index, waist and waist-to-hip ratio measures were found in males carrying the variant allele. Lower levels of liver function biomarkers were associated with the presence of the KCNJ2-A allele. Overall and in males, the variant's association to lower gamma-glutamyl transferase (GGT) levels remained significant after Bonferroni adjustments. These novel findings suggest the sour taste SNP, KCNJ2-rs236514, may be modifying macronutrient, vitamin and mineral intakes, and markers of metabolic health. Research on the extra-oral functions of this SNP may improve health outcomes for those with overweight, obesity and liver disease.


Author(s):  
Tijani Stephanie Abiola ◽  
Olori Ogaraya David ◽  
Farombi Ebenezer Olatunde

Aim: Manganese (Mn) is an essential trace element in many cellular processes. However, there is dearth of literature on its influence on indomethacin-induced hepatorenal damage. Therefore, this study was conducted to investigate the effect of manganese on indomethacin-induced hepatorenal damage in rats. Methods: Rats were divided into four groups of eight rats consisting of control group, indomethacin (IND) alone (20 mg/kg), Mn alone (10 mg/kg) and co-treated group that were treated orally for 14 consecutive days. Twenty four hours after treatment, under pentobarbital anesthesia, blood was collected and liver was excised to prepare homogenate and histology staining. Liver and kidney function tests aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), glutamine dehydrogenase (GLDH), sorbitol dehydrogenase (SDH), glucose-6-phosphate dehydrogenase (G6PD), bilirubin (BIL), urea, creatinine, cholesterol (CHOL), triglycerides (TG), low and high density lipoprotein (LDL and HDL), electrolytes and oxidative stress superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and lipid peroxidation (LPO) biomarkers were assessed. Results: The results showed that indomethacin caused hepatorenal damage in rats manifested with increase in serum hepatic and renal function biomarkers. But co-administration of IND with Mn significantly (p < 0.05) decreased the level of hepatorenal biomarkers. Additionally, co-administration of IND with Mn improved the antioxidant status with concomitant reduction of LPO and restored the integrity of the liver and kidney histologically. Conclusion: The results of this study emphasize that co-administration of IND with Mn to rats alleviated IND-induced hepatorenal toxicities and oxidative stress in rats.


2020 ◽  
Vol 18 (2) ◽  
pp. 163-170
Author(s):  
Agustina W. Djuma ◽  
Novian A. Yudhaswara ◽  
Suzanne Patricia Dardeau

East Nusa Tenggara is a province of high alcohol abuse in Indonesia. Ngada Regency has a prevalence of 38.8%. The high prevalence is inseparable from traditional factors and socio-cultural norms which strongly influence the habit of consuming alcohol, the cold temperature in this area further strengthens this habit. The impact of alcohol consumption is the emergence of various types of diseases, one of which is impaired liver function such as alcoholic liver disease. The objective of this study is to determine the relationship between alcohol consumption and impaired liver function in communities in Bajawa and Golewa Districts, Ngada Regency. This research method is an observational analytic with cross-sectional design. The research subjects were 55 people who consumed alcohol in Golewa and Bajawa Districts, who had met the inclusion criteria. Alcohol consumption was measured by the AUDIT (The Alcohol Use Disorders Identification Test) questionnaire, while the parameter for liver disorders was the level of Gamma Glutamyl Transferase (GGT). The prevalence of liver dysfunction based on GGT examination was 15%. Meanwhile, the relationship between alcohol consumption and impaired liver function was tested with the Spearman correlation with α 0.05, the correlation value was p = 0.413, which means it has a moderate or significant, not too strong relationship. It is recommended that the people of Ngada Regency reduce alcohol consumption so that it can reduce the risk of impaired liver function.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L Stolz ◽  
M Orban ◽  
N Karam ◽  
E Lubos ◽  
M Wild ◽  
...  

Abstract Background The prognostic value of impaired liver function in the presence of moderate-to-severe and severe mitral regurgitation (MR), also called cardio-hepatic syndrome (CHS), for outcomes in patients undergoing transcatheter edge-to-edge repair (TEER) has not been studied yet. Purpose In this work, we aimed at identifying the prognostic impact of the CHS on two-year all-cause mortality in patients undergoing TEER compared to established risk factors. Furthermore, we evaluated the change in hepatic function after TEER. Methods Hepatic function was assessed by laboratory parameters of liver function (bilirubin, gamma glutamyl transferase [GGT], alkaline phosphatase [AP], aspartate and alanine aminotransferase [AST and ALT]). We defined CHS as elevation of at least two out of three laboratory parameters of hepatic cholestasis (bilirubin, GGT, AP). The impact of CHS on two-year mortality was evaluated using a proportional hazards Cox model. The change in hepatic function after TEER was evaluated by repeat laboratory testing at follow-up. Results We included 1083 patients who underwent TEER for highly symptomatic primary or secondary MR at four high volume academic European centers between 2008 and 2019. In 66.4% of patients, we observed elevated levels of either bilirubin, GGT or AP. CHS was present in 23% of patients and showed strong association with a reduced two-year survival (52.9% vs. 87.0% in patients without CHS, p&lt;0.01). In a multivariate Cox regression model, CHS was identified as a strong and independent predictor of increased two-year mortality (hazard ratio 1.49, p=0.03). In patients with successful MR reduction ≤2+ (90.7% of patients), parameters of hepatic function significantly improved from baseline to follow-up (−0.2 mg/dl for bilirubin; −21 U/l for GGT, respectively, p&lt;0.01), while they did not in case of residual postprocedural MR &gt;2+. Conclusions CHS can be observed in up to 25% of patients undergoing TEER and is associated with impaired two-year survival rates. Successful TEER is associated with decreased levels of hepatic enzymes at follow-up evaluation. FUNDunding Acknowledgement Type of funding sources: None. Cardio-hepatic syndrome TEER


2021 ◽  
Author(s):  
Siqi Li ◽  
Xiaoling Liao ◽  
Yuesong Pan ◽  
Xianglong Xiang ◽  
Yumei Zhang

Abstract Background: Gamma-glutamyl transferase (GGT) can maintain the physiological concentration of glutathione in cells, and protect them from oxidative stress-induced damage. However, its role in post-stroke cognitive impairment (PSCI) remains unknown. Here, we explored the impact of serum biomarker-GGT on PSCI. Methods: We conducted a prospective, multicenter cohort study. 1, 957 participants who suffered a stroke and measured baseline GGT were enrolled from the Impairment of Cognition and Sleep (ICONS) study of the China National Stroke Registry-3 (CNSR-3). They were categorized into four groups according to the quartiles of baseline GGT levels. Cognitive function was assessed by using the Montreal Cognitive Assessment (MoCA) approach. The multiple logistic regression models were performed to evaluate the relationship between GGT and PSCI at 3 months follow-up.Results: Among 1,957 participants, 671 (34.29%) patients suffered PSCI at 3 months follow-up. The highest GGT level quartile group exhibited a lower risk of PSCI in the fully adjusted model [OR (95% CI): 0.69 (0.50-0.96)], relative to the lowest group. Moreover, incorporation of GGT to the conventional model resulted in a slight improvement in PSCI outcomes after 3 months (NRI: 12.00%; IDI: 0.30%).Conclusions: Our findings demonstrated that serum GGT level was inversely associated with the risk of PSCI, with extremely low levels acting as a risk factor for PSCI.


2016 ◽  
Vol 4 (2) ◽  
pp. 178 ◽  
Author(s):  
Mona Abdel Rasoul ◽  
Gehan Marei

This study aimed to investigate the prophylactic effect of turmeric (Curcuma longa) Rhizome Ethanolic extract (CLRE) at 250 mg/kg as antioxidant effects against penconazole induced sub-acute toxicity. Hepatic, renal and testicular pathological changes caused by oxidative damage induced by penconazole in rats were biochemically and histologically evaluated. Male rats were treated with penconazole, via oral route, at doses of 0.5 mg/ kg body weight (b.w.; acute reference dose, ARfD), 25 mg/kg b.w. (no observed adverse effects level, NOAEL) and 100 mg/ kg b.w. (1/20 lethal dose [LD50]) for 28 consecutive days. Penconazole treatments had significant (p < 0.05) and gradual reductions in body and relative testicular weight accompanied by significant elevation in the relative liver and kidney weights. Significant increase serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dhydrogenase(LDH), gamma-glutamyl transferase (GGT), creatinine (Cre), uric acid and blood glucose was observed due to penconazole treatments. However, total protein and testosterone hormone were significantly decreased. Exposure to penconazole caused increase in lipid peroxidation (LPO) and decreased of liver and kidney antioxidant enzymes activity as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Histopathological studies confirmed the ameliorative beneficial effects of turmeric biochemical parameters. On the basis of this study, the use of tumeric rhizomes as a functional food or as a nutraceutical product could be a useful approach to protect individuals who are regularly exposed to penconazole.


2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Abdel-Tawab H. Mossa ◽  
Faten M. Ibrahim ◽  
Samia M. M. Mohafrash ◽  
Doha H. Abou Baker ◽  
Souad El Gengaihi

The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg−1body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg−1body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity.


Sign in / Sign up

Export Citation Format

Share Document