Histopathological findings of renal tissue induced by oxidative stress due to different concentrations of fluoride

Abstract

It has been reported that excessive intake of fluoride can induce renal lesions. However, its pathogenesis is still less understood. Therefore, this study was conducted to investigate oxidative damage and the relationships between the oxidative damage and renal lesions in fluoride-treated mice by using the methods of histopathology, biochemistry, flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). A total of 240 ICR mice were randomly divided into four equal groups (sodium fluoride was given orally at the dose of 0, 12, 24 and 48 mg/kg body weight for 42 days, respectively). We found that fluoride in excess of 12 mg/kg induced renal oxidative damage, which was characterized by increasing the levels of reactive oxygen species (ROS) production and contents of malondialdehyde (MDA) and protein carbonyls (PC), and decreasing the abilities of anti-superoxide anion (ASA) and anti-hydroxyl radical (AHR), glutathione (GSH) content, as well as activities and mRNA expression levels of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px). Concurrently, fluoride caused degeneration and necrosis of the tubular cells, renal tubular hyaline casts and glomeruli swelling, which were consistent with the alteration of renal function parameters including elevated contents of serum creatinine (Cr), serum uric acid (UA), blood urea nitrogen (BUN), and the activities of urinary N-acetyl-b-D-glucosaminidase (NAG), renal lactate dehydrogenase (LDH), and reduced activities of sodium-potassium adenosine triphosphatase (Na+/K+-ATPase) and acid phosphatase (ACP) in the kidney. The above-mentioned results showed that fluoride in excess of 12 mg/kg induced renal oxidative damage, which then caused renal lesions and dysfunctions. These findings also clearly demonstrated that oxidative damage is one of the mechanisms of fluoride-induced renal lesions and dysfunctions.

Protective and curative effects of Boerhaavia diff usa L. against fl uoride induced renal oxidative stress and antioxidant enzymes in rats

“…The present results are in accordance with previous fl uorosis reports [3,13,19]. Decrease in the level of fl uoride after mitigation with leaf extract also resulted in signifi cant increase in content of reduced glutathione as compared with 40 days of fl uoride treatment.…”

“…Fluoride reacts with polyunsaturated fatty acids and initiates lipid peroxidation leading to necrosis and apoptosis [1,2]. As the primary organ concerned with excretion and retention of fl uoride, kidney is quite sensitive to the toxicity of fl uoride [3]. The situation of serious imbalance between oxidant and antioxidant is referred to as oxidative damage.…”

Combination of Fluoride and SO2 Induce DNA Damage and Morphological Alterations in Male Rat Kidney

“…Depending on the traits of systemic toxins, these two systemic toxins can damage the renal tissue [1,8]. In a recent study, the morphological alterations such as degeneration, necrosis of the tubular cells, renal tubular hyaline casts and swollen glomeruli abnormalities were detected in 12, 24, 48 mg/kg body weight NaF exposure mice after 42 days [27]. Interestingly, a previous study reported that, NaF could reduce the integrity of tight connections in M-1 cell monolayers of mice [28].…”

Copper Induces Oxidative Stress and Apoptosis in the Mouse Liver

“…The liver samples (n = 8 per group, half male and female) were rinsed in chilled saline solution, weighed and homogenized in nine volumes of ice-cold 0.9% NaCl solution, and centrifuged at 3500 rpm for 10 min at 4°C. The supernatants were collected for detecting the activities of CAT, GR, SOD, GST, GSH-Px, ASA, and AHR, as well as contents of GSH, MDA, and PC in the liver by biochemical methods according to the instructions of the reagent kits [27].…”