Oxidative stress and apoptotic changes in primary cultures of rat proximal tubular cells exposed to lead

Abstract

Lead is a known nephrotoxic element. In this study, primary cultures of rat proximal tubular (rPT) cells were treated with different concentrations of lead acetate (0.25, 0.5 and 1 microM) to investigate its cytotoxic mechanism. A progressive loss in cell viability together with a significant increase in the number of apoptotic and necrotic cells and lactate dehydrogenase release were seen in the experiment. Simultaneously, elevation of reactive oxygen species levels and intracellular [Ca(2+)]i, depletion of mitochondrial membrane potential and intracellular glutathione were revealed during the lead exposure. In addition, apoptotic morphological changes induced by lead exposure in rPT cells were demonstrated by Hoechst 33258 staining. The apoptosis was markedly prevented by N-acetyl-L-cysteine, while the necrosis was not affected. Moreover, catalase and superoxide dismutase activities in the living cells rose significantly. In conclusion, exposure of rPT cells to low-concentration lead led to cell death, mediated by an apoptotic and a necrotic mechanism. The apoptotic death induced by oxidative stress was the chief mechanism. Meanwhile, a group of cells survived lead action, mediated by their ability to activate antioxidant defense systems.

Effect of Testosterone on Lead Acetate Toxicity in Male Albino Rats

“…Besides that hypogonadism is a clinical condition in which low levels of serum testosterone are found in association with specific signs and symptoms. When hypogonadism occurs in an older man, the condition is often called andropause or androgen deficiency of the aging male or late onset hypogonadism [16]. Previous study showed that castration increased lipid peroxidation and consequently reduced glutathione in both liver and kidney [17].…”

“…It has been reported that L.A. causes mitochondrial damage, uncoupling of the respiratory chain and cell death [16]. Another histological indication of lead toxicity in the kidney is the karyomegaly of tubular cells [27].…”

Overexpression of Ref-1 Inhibits Lead-induced Endothelial Cell Death via the Upregulation of Catalase

“…A number of studies have revealed that lead exposure is capable of inducing cell death in a variety of cell types (Fox et al, 1998;Cheng et al, 2002;Wang et al, 2009). Even though the mechanisms relevant to lead-induced cell death have yet to be fully elucidated, some have implied a relationship between oxidative stress and cell death in lead-induced cell death.…”

Selenium: an element with two faces

“…The reason was consumption of plants containing high levels of selenium. Symptoms of selenosis in humans are similar to those observed in the horses of Fort Randall: fatigue, hair loss, gastrointestinal symptoms, liver damage, and neurological and CNS symptoms, including aggressiveness.Selenium (Brozmanová et al 2010;Valdiglesias et al 2010; Grotto et al 2009a, b) and oxidative as well as antioxidative mechanisms in general (Bolt and Hengstler 2010;Nishimura et al 2010;Cederbaum et al 2009; Grotto et al 2009a, b;Hewitt et al 2007;Wang et al 2009;Glahn et al 2008) represent cutting-edge topics in toxicology. Therefore, the editors are pleased that Cristina W Nogueira and Joao BT Rocha from Santa Maria University in Brazil have accepted our invitation to contribute a comprehensive review on the pharmacology and toxicology of selenium and organoselenium compounds (Nogueira and Rocha 2011).…”