Nephrotoxicity of cisplatin (CP) involves renal oxidative stress and inflammation, and sesamin (a major liganin in many plants) has strong antioxidant and antiinflammatory actions. Therefore, we investigated here the possible mitigative action of sesamin on CP nephrotoxicity in rats. Sesamin was given orally (5 mg/kg/day, 10 days), and on the 7th day, some of the treated rats were injected intraperitoneally with either saline or CP (5 mg/kg). On the 11th day, rats were sacrificed, and blood and urine samples and kidneys were collected for biochemical estimation of several traditional and novel indices of renal damage in plasma and urine, several oxidative and nitrosative indices in kidneys, and assessment of histopathological renal damage. CP significantly and adversely altered all the physiological, biochemical and histopathological indices of renal function measured. Kidneys of CP‐treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with sesamin. Sesamin treatment did not significantly alter the renal CP concentration. The results suggested that sesamin had ameliorated CP nephrotoxicity in rats by reversing the CP-induced oxidative stress and inflammation. Pending further pharmacological and toxicological studies sesamin may be considered a potentially useful nephroprotective agent.
The effects of the nephrotoxic, anticancer agents cisplatin (CDI)P) and carboplatin (CBDCA), and the free radical scavenger, stobadine, were investigated on lipid peroxidation (EI’O) of rat kidney homogenates and phosphatidylcholine (PC) liposomes. Kidney homogenates were incubated in air at 37 °C for 6-48 h and lipid peroxidation was detected spectroscopically as absorbance (533 nm) of the thiobarbituric acid- malondialdchyde (TBA-MDA) complex. CDDP (0.3-10 mmol.I'1) increased LPO of the homogenate. CBDCA decreased the TBA-MDA absorbance, yet was found to interfere with MDA, TBA and/or with the TBA-MDA complex. Thus when CBDCA is involved, the TBA- MDA method for detection of LPO is not suitable. Stobadine (0.1 mmol.I'1 ar>d 1 mmol.I1) inhibited LPO either in the control homogenate and in the homogenate where peroxidation was increased by CDDP. The effect of CDDP and CBDCA on peroxidation of PC liposomes was monitored as oxygen consumption using a Clark-type oxygen electrode. CDDP increased but CBDCA decreaed the rate of oxygen consumption during the peroxidation of liposomes induced by FcSO,». The results suggest that the effects of CDDP and CBDCA on LPO may be linked with their nephrotoxicity.
We have previously shown that chronic renal failure in rats induces changes in motor activity and behavior. Similar work on the possible effects of acute renal failure (ARF) induced by cisplatin (CP) is lacking. This is the subject matter of the current work. CP was injected intraperitoneally (i.p.) at a single dose of 20 mg/kg to induce a state of ARF, and three days later, its effects on motor activity, thermal and chemical noci ceptive tests, neuromuscular coordination, pentobarbitone-sleeping time, exploration activity and tw o depression models were investigated. The platinum concentration in the kidneys and brains of mice was also measured. The occurrence of CP-induced ARF was ascertained by standard physiological, biochemical and histo-pathological methods. CP induced all the classical biochemical, physiological and histopathological signs of ARF. The average renal platinum concen tration of CP-treated mice was 5.16 ppm, but there was no measurable concentration of platinum in the whole brains. CP treatment significantly decreased motor and exploration activities, and increased immobility time in depression models, suggesting a possible depression-like state. There was also a significant decrease in neuromuscular coordination in CP-treated mice. CP, given at a nephrotoxic dose, induced several adverse motor and behavioral alterations in mice. Further behavioral tests and molecular and biochemical investigations in the brains of mice with CP-induced ARF are warranted., B. H. Ali ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Cisplatin is a commonly used chemotherapeutic drug. It is known
for its nephrotoxic side effects with an increased risk of acute
kidney injury. Finding of clinically feasible cisplatin nephrotoxicity
markers is of importance. In our study, we compared neutrophil
gelatinase-associated lipocalin (NGAL) in serum and urine, the
estimated glomerular filtration rate (based on serum cystatin C)
and urine albumin as markers of nephrotoxicity. The study
involved 11 men and 9 women (mean ± SD age 58.2 ± 9.5 years)
with different malignancies treated with cisplatin in four cycles of
chemotherapy (I – IV). Samples 0-4 were taken before,
immediately after, in 3, 6 and 24 hours after administering
chemotherapy. We detected significant increase of ACR in
Sample 2 (p=0.03) and decrease of eGFR in Sample 4 (p=0.03)
up to 24 hours after cisplatin administration in the first
chemotherapy cycle only. When cumulative effect of cisplatin was
assessed, significantly increased values of urine albumin (vs cycle
I) were found in Sample 0 (p=0.00058), 1 (p=0.00256),
2 (p=0.00456), 3 (p=0.00006) and 4 (p=0.00319) in cycles II to
IV. We found a correlation between values of urine NGAL and
urine albumin (r=0.68, p<0.0001). In conclusion, urine albumin
was the only measured marker that consistently and statistically
significantly increased after cisplatin containing chemotherapy
cycles.