Nephrotoxicity is associate adverse effect of the anticancer drugs for solid and hematologic malignancies (Kintzel, 2001). Cisplatin, cisplatinum or cis-diamminedichloroplatinum (II) , a platinum-based drug, is one of the most frequently used anti-neoplastic agents. It has a potent anti-tumor action against wide range of malignancies, including testicular, ovarian, cervical, bladder and lung cancers as well as solid tumors resistant to other treatment regimens (Hanigan and Devarajan, 2003). The kidney is not only responsible for the excretion of cisplatin, but is also the primary site of its accumulation (Miller et al., 2010). Although several strategies have been suggested to prevent this adverse effect, no specific treatments are currently
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It is a precursor for the coenzyme ß-nicotinamide adenine dinucleotide (NAD+), which serves as an essential nutrient for cellular growth and participates in the regulation of multiple cellular functions including apoptosis (Klaidman et al., 1996; Mukherjee et al., 1997). Nicotinamide has been reported to exert a number of physiological and pharmacological effects including prevention of ATP depletion, inhibition of poly ADP- ribose polymerase (PARP), prevention of apoptosis and suppression of lipid peroxidation (Ogata et al., 2002; Klaidman et al., 2003). Also, it has been shown that nicotinamide exerts the anti-inflammatory properties both in-vitro and in-vivo. (Fernandes et al., …show more content…
Renal lipid peroxidation product, malondialdehyde (MDA) was measured in renal tissue homogenates by the method described by Ellman (1959), superoxide dismutase (SOD) activity was estimated according to Beauchamp and Fridovich (1971) and glutathione peroxidase (GPx) activity was measured according to Flohé and Gunzler (1984) using commercially available diagnostic kits from Biodiagnostic Company, Giza, Egypt.
Levels of interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha (TNF-α) in supernatants from kidney tissue homogenates were quantitated by enzyme-linked immunosorbent assay (ELISA) using Quantikine rat specific kits; R&D Systems Inc., Minneapolis, Minnesota, USA, which were obtained from Clinilab Company, Cairo, Egypt, according to manufacturer’s directions.
2.6. Histopathological Evaluation of the Kidney:
Kidneys were fixed in paraformaldehyde (4%) and embedded in paraffin. Tissue sections (4µm) were placed on slides, stained with hematoxylin and eosin (H&E) and the morphology was analyzed under light microscopy. Tubular injury was assessed using semi-quantitative scale (Ramesh and Reeves, 2004). Scores was assigned according to the percentage of cortical tubules having epithelial necrosis as follows: 0, 0%; 1, < 10%; 2, 10%- 25%; 3, 26%-75%; or 4, > 75%. Ten fields per kidney under high-power magnification were assessed and then assigned as necrosis severity
It is a precursor for the coenzyme ß-nicotinamide adenine dinucleotide (NAD+), which serves as an essential nutrient for cellular growth and participates in the regulation of multiple cellular functions including apoptosis (Klaidman et al., 1996; Mukherjee et al., 1997). Nicotinamide has been reported to exert a number of physiological and pharmacological effects including prevention of ATP depletion, inhibition of poly ADP- ribose polymerase (PARP), prevention of apoptosis and suppression of lipid peroxidation (Ogata et al., 2002; Klaidman et al., 2003). Also, it has been shown that nicotinamide exerts the anti-inflammatory properties both in-vitro and in-vivo. (Fernandes et al., …show more content…
Renal lipid peroxidation product, malondialdehyde (MDA) was measured in renal tissue homogenates by the method described by Ellman (1959), superoxide dismutase (SOD) activity was estimated according to Beauchamp and Fridovich (1971) and glutathione peroxidase (GPx) activity was measured according to Flohé and Gunzler (1984) using commercially available diagnostic kits from Biodiagnostic Company, Giza, Egypt.
Levels of interleukin (IL)-6, IL-10 and tumor necrosis factor-alpha (TNF-α) in supernatants from kidney tissue homogenates were quantitated by enzyme-linked immunosorbent assay (ELISA) using Quantikine rat specific kits; R&D Systems Inc., Minneapolis, Minnesota, USA, which were obtained from Clinilab Company, Cairo, Egypt, according to manufacturer’s directions.
2.6. Histopathological Evaluation of the Kidney:
Kidneys were fixed in paraformaldehyde (4%) and embedded in paraffin. Tissue sections (4µm) were placed on slides, stained with hematoxylin and eosin (H&E) and the morphology was analyzed under light microscopy. Tubular injury was assessed using semi-quantitative scale (Ramesh and Reeves, 2004). Scores was assigned according to the percentage of cortical tubules having epithelial necrosis as follows: 0, 0%; 1, < 10%; 2, 10%- 25%; 3, 26%-75%; or 4, > 75%. Ten fields per kidney under high-power magnification were assessed and then assigned as necrosis severity