The para isomer of dinitrobenzene disrupts redox homeostasis in liver and kidney of male wistar rats

Abstract

Background: Para-Dinitrobenzene (p-DNB) is one of the isomers of dinitrobenzene which have been detected as environmental toxicants. Skin irritation and organ toxicities are likely for industrial workers exposed to p-DNB. This study evaluated the effect of sub-chronic exposure of rats to p-DNB on cellular redox balance, hepatic and renal integrity.

Methods: Forty eight male Wistar rats weighing 160-180 g were administered 50, 75, 1000 and 2000 mg/kg b.wt (body weight) of p-DNB or an equivalent volume of vehicle (control) orally and topically for 14 days. After the period of treatment, the activities of kidney and liver catalase (CAT), alkaline phosphatase (ALP) and superoxide dismutase (SOD) as well as extent of renal and hepatic lipid peroxidation (LPO) were determined. Serum ALP activity and plasma urea concentration were also evaluated.

Results: Compared with control animals, p-DNB -administered rats showed decrease in the body and relative kidney and liver weights as well as increased renal and hepatic hydrogen peroxide and lipid peroxidation levels accompanied by decreased superoxide dismutase and catalase activities. However, p-DNB caused a significant increase in plasma urea concentration and serum, liver and kidney ALP activities relative to control. In addition, p-DNB caused periportal infiltration, severe macro vesicular steatosis and hepatic necrosis in the liver.

Conclusions: Our findings show that sub-chronic oral and sub-dermal administration of p-DNB may produce hepato-nephrotoxicity through oxidative stress.

Keywords: ALP, alanine phosphatase; CAT, Catalase; Environmental toxicants; GSH, glutathione; GST, glutathione –s –transferase, GPX, glutathione reductase, NIH, national institute of health; H&E, hamatoxilin eosin; Kidney; LPO, lipid peroxidation; Liver; MDA, malodialdehyde; OECD, Organisation for economic co-operation and Development; Oxidative stress; PHS, public health service; SOD, Superoxide dismutase; SPSS, Statistical Pucteage for Social Sciences; Sub-dermal; TBA, thiobarbituric acid; TNB, trinitrobenzene; o-DNB, ortho-dinitrobenzene, m-DNB, meta-dinitrobenzene; p-DNB, para-dinitrobenzene; p‐DNB.

Fig. 1

Catalase activity (µmol H₂O₂ consumed/min/mg protein) in the liver and kidney of rats after 14 days of oral and dermal administration.

Fig. 2

Superoxide dismutase activity (Units per milligram protein) in liver and kidney of rats treated with p-DNB for 14 days after oral and dermal administration.

Fig. 3

Lipid peroxidation levels (unit/g tissue 10^×6) in liver and kidney of rats after 14 days of oral and dermal administration of p-DNB.

Fig. 4

Effects of p-DNB on activities of ALP (U/l) in Kidney, Serum and liver of treated rats following oral and dermal administration.

Fig. 5

Photomicrograph of liver section after oral administration showing A(control): normal liver architecture, central venules, sinusoids without infiltration of inflammatory cells and hepatocytes morphology. B,C(50,75 mg/kg bwt p-DNB): poor liver architecture, moderate periportal infiltration, moderate peri vascular infiltration of inflammatory cells, tissue degeneration with loss of liver plates, severe macro vesicular steatosis with the fat fully infiltrating the cytoplasms of the liver cells and few apoptotic cells (X400).

Fig. 6

Photomicrograph of liver section after dermal administration showing (A control): normal liver architecture, hepatocytes, central venules, sinusoids without infiltration of inflammatory cells. B,C (1000, 2000 mg/kg bwt p-DNB): poor liver architecture, aggregating inflammatory cells, liver parenchyma with fibrosis and hepatic necrosis, severe micro vesicular steatosis with the fat infiltration within the cytoplasms. (X400).