Objectives: The present experimental study was designed to evaluate the impact of prophylactic curcumin (CUR) on chronic adriamycin (ADR) exposure-induced structural renal alterations.
Materials & Methods: The study comprised 30 normal healthy growing male albino rats divided into 3 groups: Control group given distilled water, ADR group injected once intraperitoneally by ADR in a dose of 50 mg/kg, 5 rats were sacrificed every 2 weeks after injection (ADR-2, ADR-4 & ADR-6) and CUR group included 15 rats received 200 mg/kg body weight of curcumin in 1% gum acacia, orally for 7 days before intraperitoneal injection of ADR in dose of 50 mg/kg and daily thereafter throughout the study and 5 rats were sacrificed every 2 weeks after injection (CUR-2, CUR-4 & CUR-6). Kidney tissue was obtained for histological studies using hematoxylin and eosin (Hx & E) and Masson’s trichrome stains. Immunohistochemical and morphometric study to determine golmerular area cortical and medullary connective tissue percentage and the count of PCNA +ve endothelial, mesangial and interstitial nuclei.
Results: There was time-course progression of harmful effect of ADR on renal structure manifested as minimal congested renal glomeruli and interstitial congestion in ADR-2 specimens progressed in ADR-4 specimens to congested glomeruli with narrowing extending to partial obliteration of Bowman's space but in ADR-6 group, there were multiple shrunken and congested renal glomeruli with vacuolation of cytoplasm of the lining cells of the proximal tubules and intense mononuclear cellular infiltration. Minimal glomerular and interstitial congestion with preserved Bowman's space and no obvious cellular infiltration was reported in CUR-2 and CUR-4 groups, and CUR-6 rats showed picture comparable to control animals apart from mild congestion and occasional shrunken glomeruli with preserved Bowman's space and minimal cellular infiltration. In Masson's Trichrome stained sections, ADR-4 specimens showed focal dense fibrous bands that become dense in ADR-6 group, while few thin bands between the proximal tubules were detected in CUR-6 specimen. Multiple PCNA +ve rounded nuclei of mesangial cells were detected among the +ve flattened endothelial nuclei in glomeruli recruiting obliterated Bowman's space in ADR-4 group and in the shrunken glomeruli of ADR-6 specimens, while were occasional in CUR-6 group. Areas of PCNA +ve nuclei were detected between the proximal tubules were detected in ADR-4 groups and detected in wider areas in ADR-6 group, while group CUR-6 showed smaller areas of +ve flattened nuclei than in ADR-6. Mean glomerular area was significantly larger and smaller in groups ADR-4 and ADR-6 compared to groups CUR-4 and CUR-6, respectively. Both cortical and medullary connective tissue percentage were significantly higher in ADR-4 and ADR-6 groups compared to control group and compared to CUR-4 group both cortical and medullary connective tissue areas were significantly higher in ADR-4 group. Compared to control, mean PCNA positive nuclei of endothelial cells was significantly lower in ADR-6 animals, but mean PCNA positive nuclei of mesangial cells was significantly higher in ADR-4 and ADR-6. Mean positive PCNA count in nuclei of interstitial cells of ADR-6 animals was significantly higher compared to ADR-4 and CUR-6 animals, no positive PCNA nuclei were detected in interstitial cells in other groups.
Conclusion: It could be concluded that prophylactic administration of curcumin could ameliorate the nephrotoxic effects of chronic treatment with adriamycin and was recommended in the tried dose for patients assigned to adriamycin treatment. |
