NEPHROTOXICITY INDUCED DUE TO NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) & ARSENIC

 

About Authors:
Varsha Tanaji Jadhav1*, 2Joyeeta Sanyal
Cilicant Chem.Pvt.Ltd., Microbiologist, Pune
Rasayani Biologic.Ltd., Microbiologist
*varsha.jadhav6@gmail.com

Abstract:-
Nephrotoxcity is the injury or damage to the one or both of the kidneys due to a toxic material. Usually toxic material taken orally results in nephrotoxicity. The kidneys are the most essential organs of the urinary system. They are responsible for the quality, quantity and filtration of the fluids in the body. Every day, the kidneys filter about 180 litres of blood, and about four times as much as the amount that passes through any other organ. Hence the kidneys are more often exposed to toxic substances in the blood and are very vulnerable to damage from those materials. They also help to control blood pressure and other direct cell activities and homeostasis as they produce vitamins and hormones for example hormones erythropoietin, rennin. Other important functions performed by them are regulation of calcium, chloride, sodium ions, and pH control (Taferner B, et al., 2009). The kidneys functional units are the nephrons. Diseases of the kidney are diverse, but they commonly display some characteristic clinical features. These include chronic diseases, acute injuries, urinary tract obstruction and infection, renal damage or failure. Epidemiological results suggest that environmental toxins like heavy metals plays significant role in the development of these diseases. Particularly large amounts of these are disposed of as industrial by-products which are not biodegradable. The incidences of chronic and acute renal failures have risen in past few years. In the America only, kidney diseases are the ninth leading cause of death (Ernesto Sabath et al., 2012). Hence identifying the risk factors associate with these diseases is important to prevent it.This report aims to discuss the physiopathological mechanisms and the consequences of kidney injury due to arsenic and Non Steroidal Anti Inflammatory Drugs (NSAID).


REFERENCE ID: PHARMATUTOR-ART-1838

Introduction:-
Arsenic Nephrotoxicity:-

Arsenic is one of the most widely spread environmental pollutant, and millions of people mainly in Asia and Latin America suffer from its exposure. It is the commonly spread in drinking water via industrial wastes. Approximately average daily human exposure of arsenic is 20µg via food and water (WHO, 2001).Other forms of the exposure are the medicines used in treatment of cancer, sleeping sickness, and compounds used in Silicon-based computer chips, manufacturing of glass, feed additive (poultry and swine), and wood preservative(Jarup, 2003).

Clinical manifestations:-
Since ancient times in organic arsenic has been recognized as human poison. Periodically arsenic related consequences have been reviewed. The arsenic toxicity is systematic and involves number of organ system. These effects can be acute, sub-acute and chronic as well (Chen et al., 1997). The acute and sub acute effects of the arsenic toxicity are shown in the table 1

Table 1 Acute and Sub acute Toxicity of Arsenic
(Source: -
WHO, 1981, 2001; ATSDR, 2005, Chen et al. 1997)

Most studies on arsenic do not have exact details of dose response relationship details. Inorganic arsenic is easily absorbed from intestine compared to the organic one. Earliest symptoms of acute toxicity are dry mouth and burning lips. The sites of kidney damage are glomeruli, capillary and tubules (Chen et al., 1997). As the kidneys are affected, it shut downs there is no hemodynamic balance. It results innecrosis and rapid cell death. Hyperkeratosis or Blackfoot disease is characteristic vascular disease due to arteriosclerosis, is observed in long term exposure to arsenic (Figure1). It binds to red blood cells andsulfhydryl-containing proteins. The literature does not offer much information on manifestations of arsenic toxicity in the kidneys. But on the basis of available data it concludes that it results in damage to tubules, low molecular weight proteinuria, glycosuria, aminoaciduria and deterioration of renal function (Huang M et al., 2009). It affects the filtration process, salt and water balance in the body due to injury to the kidneys.Hence long term effects are mostly seen on the cardiovascular system. Table 2 shows the chronic long term effects of the arsenic via ingestion and inhalation.


Table 2 Chronic Cardiovascular toxicity of arsenic
(Chen et al., 1997 Chen et al., 2005
, ATSDR, 2005)

It has been classified as the group 1 carcinogen based on the literature studies. It shows the significant amount of dose- response relationship in long term exposure between the arsenic in the drinking water and increased risk of cancers lesions in the liver, kidney, skin, urinary bladder, lungs and nasal cavities (IARC, 2004, 2006).

Mechanism of Arsenic Nephrotoxicity:-

Figure 2 Mechanism of arsenic induced kidney injury
(
Ernesto Sabath et al., 2012)

As arsenic is absorbed in the intestine, lungs (inhalation) and in some amount in skin it is transformed from the less toxic pentavalent form to more toxic trivalent form in liver and renal tubules in kidneys (Ellenhorn MJ et al., 1988). Arsenic is methylated in the liver via glutathione (GSH) process which leads to its excretion via biliary excretion (Fig2). In the intracellular medium these are transported in via aquaglyceroporins AQ3 and AQ9. This process causes results in the accumulation of arsenic ions and ultimately results in there excretion. But if there is glutathione stores (GSH) depletion in the body, it results in increase in the oxidative activity reactive free radicals (Carbrey et al., 2009). Another group proteins which are also involved in this process are multi drug resistance proteins (MRP 1-2).These are involved in the transport of arsenic from glutathione (GSH) to the bile for excretion. Binding to the thiol groups causes activation of signal cascade, impairment of antioxidant defence mechanism and triggers apoptosis (Flora et al., 2008).

There have been many cases of toxicity associated with heavy metals. As these are commonly found in our living environment and there are only few treatment options on them, so public awareness should be made to reduce the usage and to limit their exposure. Every precautionary step and safety recommendations while handling heavy metals should be followed.

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