Metal-induced nephrotoxicity to diabetic and non-diabetic Wistar rats

Riaz, Muhammad; Nisa, Zaib Un; Mehmood, Azra; Anjum, Muhammad Sohail; Shahzad, Khurram

doi:10.1007/s11356-019-06022-z

Cited by 27 publications

(21 citation statements)

References 54 publications

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“…[12][13][14][15][16][17][18][19] There are numerous animal models that have been used to elucidate the pathological mechanisms of kidney disease. [19][20][21] Those induced by ischemia, 14,22,23 lipopolysaccharide, [24][25][26][27] cisplatin, [28][29][30] arsenic, [31][32][33] adenine, [34][35][36] cadmium 15,[37][38][39][40] and diabetes [41][42][43][44][45][46] are widely used as animal models of kidney disease. These models have also been used to test the therapeutic effect of a given drug or compound.…”

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confidence: 99%

Folic acid‐induced animal model of kidney disease

2021

Anim Models and Exp Med

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Kidney disease may be generally classified clinically into two categories: acute kidney injury (AKI) and chronic kidney disease (CKD), both of which are tightly interconnected. 1-3 AKI can often develop in clinical settings in critically ill patients, leading to increased morbidity and mortality. 4,5 AKI is manifested by a rapid decline in the glomerular filtration rates (GFRs) 6 and its pathogenesis is complex, involving ischemia, sepsis, drug toxicity, and trauma. 7 If left unmanaged, AKI can develop into CKD, which is characterized by a progressive decrease in GFR, culminating in a gradual loss of renal function. 8 The transition from AKI to CKD can also be hastened by numerous risk factors such as obesity, hypertension, diabetes, and chronic inflammation. 9-11 Currently, there are no effective treatments for either AKI or CKD, stressing a continual need to elucidate the underlying pathological mechanisms of AKI and CKD. In this regard, animal models of kidney disease have been invaluable in that utilization of these animal models not only facilitates our understanding of the

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confidence: 99%

Folic acid‐induced animal model of kidney disease

2021

Anim Models and Exp Med

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“…Previously, we reported metal-induced nephrotoxicity using diabetic and non-diabetic Wistar rats 22 . Here, we extended our analysis employing histopathological and qRT-PCR (for Bcl 2 and Caspase-3 expression) analyses to investigate the metal alone as well as metal mixture induced toxicity in different organs including heart, liver, pancreas, and spleen in addition to the kidney of diabetic and non-diabetic Wistar rats.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we reported metal-induced nephrotoxicity in diabetic and non-diabetic Wistar rats 22 . Here, we aimed to investigate the effects of metal alone as well as metal mixture (Pb, Cd, Mn, and As) induced toxicity in different body organs including heart, liver, pancreas, spleen, and kidney at molecular level in diabetic and non-diabetic Wistar rats using histopathology and quantitative real-time PCR (qRT-PCR) analyses.…”

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confidence: 92%

Assessment of metals induced histopathological and gene expression changes in different organs of non-diabetic and diabetic rats

Riaz

Nisa

Anjum

et al. 2020

Sci Rep

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Diabetes is a complex metabolic disorder and different environmental toxicants including heavy metals have been involved in diabetes induction. Therefore, assessment of the environmental risk factors and heavy metals induced toxicity have become critical for reducing the consequences of metals pollutants. Previously, we reported heavy metals induced nephrotoxicity in non-diabetic and diabetic rats. Here, we extended our analysis by examining the heavy metals induced organs (heart, kidney, liver, pancreas, and spleen) damage in diabetic and non-diabetic Wistar rats using histopathology and quantitative real-time PCR (qRT-PCR). Following the generation of the diabetic rat model, the animals were exposed to heavy metals including lead (Pb), arsenic (As), manganese (Mn) and cadmium (Cd). Both non-diabetic and diabetic rats were exposed to heavy metals for 30 days and subsequently, the heart, kidney, liver, pancreas and spleen tissues were examined. Heavy metal treatment resulted in irregularly arranged myofibrils and vacuolization in the heart tissue of metal treated groups as evident from hematoxylin and eosin (H & E) staining. The kidney tissue of rats treated with heavy metals showed tubular degeneration, fibrosis, hemorrhage, and vacuolation. The liver of the heavy metals treated rats exhibited cellular degeneration and necrosis. The pancreatic tissue of streptozotocin injected untreated and metal treated rats revealed severe degeneration, necrosis, degranulation, shrinkage, and depression in the islets of Langerhans. Increased red pulp area and congestion were observed in the spleen of the metal mixture treated non-diabetic and diabetic rats. In line with the histological data, the qRT-PCR analysis showed downregulated expression of Bcl 2 and upregulation of Caspase-3 in nondiabetic and diabetic metal treated rats as compared to the non-diabetic untreated rats. In conclusion, the present study revealed, diabetic rats are more prone to metal alone as well as metal mixture induced organ damage as compared to non-diabetic rats. Diabetes is a metabolic disorder, characterized by impaired insulin secretion, fasting hyperglycemia or insulin receptor insensitivity. The prevalence of diabetes is increasing all over the world and increased from 4.7% in 1980 to 8.5% in 2014 1. Diabetes is the 7 th leading cause of mortality in the United States and worldwide and results in serious complications including kidney disease, cardiovascular disease, blindness, etc. 1,2. It is well documented that environmental exposure to synthetic or naturally occurring chemical elements contribute to diabetes induction 3-5. Metals are essential components of biological functions, while their higher concentrations can be toxic 6,7. Cadmium (Cd), arsenic (As), cobalt (Co), mercury (Hg), manganese (Mn) and lead (Pb) are known as endocrine-disrupting chemicals 8,9. Importantly, Pb, As, Mn and Cd play a crucial role in public health issues 10 .

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“…Human exposure to heavy metals; such as cobalt (Co 3+ ), mercury (Hg 2+ ), lead (Pb 2+ ), chromium (Cr 4+ ) and iron (Fe 2+ ), is strongly associated with renal diseases [ 130 , 131 , 132 ]. Nitrilotriacetate (Fe-NTA) is a strong oxidant and potent nephrotoxic agent which generates highly reactive hydroxyl radical causing injuries of various organs, including kidneys.…”

Section: Renoprotective Effects Of Luteolin Against Nephrotoxic Subst...mentioning

confidence: 99%

Renoprotective Effects of Luteolin: Therapeutic Potential for COVID-19-Associated Acute Kidney Injuries

et al. 2022

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Acute kidney injury (AKI) has been increasingly reported in critically-ill COVID-19 patients. Moreover, there was significant positive correlation between COVID-19 deaths and renal disorders in hospitalized COVID-19 patients with underlying comorbidities who required renal replacement therapy. It has suggested that death in COVID-19 patients with AKI is 3-fold higher than in COVID-19 patients without AKI. The pathophysiology of COVID-19-associated AKI could be attributed to unspecific mechanisms, as well as COVID-19-specific mechanisms such as direct cellular injury, an imbalanced renin-angiotensin-aldosterone system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. To date, there is no specific treatment for COVID-19 and its associated AKI. Luteolin is a natural compound with multiple pharmacological activities, including anticoronavirus, as well as renoprotective activities against kidney injury induced by sepsis, renal ischemia and diverse nephrotoxic agents. Therefore, in this review, we mechanistically discuss the anti-SARS-CoV-2 and renoprotective activities of luteolin, which highlight its therapeutic potential in COVID-19-AKI patients.

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Metal-induced nephrotoxicity to diabetic and non-diabetic Wistar rats

Cited by 27 publications

References 54 publications

Folic acid‐induced animal model of kidney disease

Folic acid‐induced animal model of kidney disease

Assessment of metals induced histopathological and gene expression changes in different organs of non-diabetic and diabetic rats

Renoprotective Effects of Luteolin: Therapeutic Potential for COVID-19-Associated Acute Kidney Injuries

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