Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats

Ehsan, N.; Ijaz, M. U.; Ashraf, A.; Sarwar, S.; Samad, A.; Afzal, G.; Andleeb, R.; Al-Misned, F. A.; Al-Ghanim, K. A.; Ahmed, Z.; Riaz, M. N.; Mahboob, S.

doi:10.1590/1519-6984.243438

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Brazilian Journal of Biology

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Original Article • Braz. J. Biol. 83 • 2023 • https://doi.org/10.1590/1519-6984.243438 copy

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats

Mitigação da nefrotoxicidade induzida pela cisplatina pela casticina em ratos albinos machos

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H₂O₂) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Keywords:
cisplatin; renal damage; casticin; curative potential

Groups	CAT (U/mg protein)	SOD (nanomole)	POD (U/mg protein)	GST (mg/dl)	GSR (Nm NADPH oxidized/min/mg tissues)	GSH (nM/min/mg protein)
Control	6.49 ± 0.09 ^a	7.25 ± 0.06 ^a	5.64 ± 0.03 ^a	22.09 ± 0.62 ^a	2.94 ± 0.04 ^a	14.7 ± 0.38 ^a
CP (10 mg/kg)	2.45 ± 0.06 ^b	3.69 ± 0.09 ^b	1.90 ± 0.02 ^b	10.40 ± 0.31 ^b	0.97 ± 0.03 ^b	7.78 ± 0.27 ^b
CP (10 mg/kg) + CAS (50 mg/kg)	6.22 ± 0.04 ^a	6.91 ± 0.03 ^c	5.10 ± 0.01 ^a	20.49 ± 0.39 ^c	2.75 ± 0.02 ^a	13.7 ± 0.29 ^c
CAS (50 mg/kg)	6.47 ± 0.01 ^a	7.40 ± 0.01 ^a	5.61 ± 0.04 ^a	22.84 ± 0.14 ^a	3.06 ± 0.03 ^a	14.6 ± 0.19 ^a

Groups	TBARS (nM/mg tissue)	H₂O₂ (µM/min/mg protein)
Control	15.36 ± 0.42 ^a	1.19 ± 0.09 ^a
CP (10 mg/kg)	24.89 ± 0.24 ^b	5.63 ± 0.07 ^b
CP (10 mg/kg) + CAS (50 mg/kg)	16.23 ± 0.21 ^c	1.93 ±0.05 ^a
CAS (50 mg/kg)	15.29 ± 0.19 ^a	1.24 ± 0.07 ^a

Groups	Control	CP (10 mg/kg)	CP (10 mg/kg) + CAS (50mg/kg)	CAS (50mg/kg)
Urea (mg/dl)	20.6 ± 0.35 ^a	66.7 ± 0.60 ^b	26.6 ± 0.32 ^c	21.7 ± 0.31 ^a
Creatinine (mg/dl)	1.94 ± 0.06 ^a	4.29 ± 0.13 ^b	2.21 ± 0.01 ^c	2.04 ± 0.04 ^a
Creatinine clearance (ml/min)	1.62 ± 0.06 ^a	0.92 ± 0.03 ^b	1.53 ± 0.01 ^c	1.57 ± 0.01 ^ac
Albumin (mg/dl)	8.07 ± 0.05 ^a	3.67 ± 0.04 ^b	7.91 ± 0.02 ^c	8.01 ± 0.04 ^ac
Urobilinogen (mg/dl)	3.66 ± 0.03 ^a	9.98 ± 0.03 ^b	4.05 ± 0.03 ^c	3.97 ± 0.02 ^a
Urinary proteins (mg/dl)	14.7 ± 0.22 ^a	33.6 ± 0.82 ^b	17.0 ± 0.08 ^c	15.3 ± 0.15 ^a
Urinary KIM-1 (mg/ml)	0.42 ± 0.01 ^a	2.22 ± 0.05 ^b	1.17 ± 0.05 ^c	0.44 ± 0.02 ^a
NGAL (ng/day)	0.83 ± 0.03 ^a	2.86 ± 0.06 ^b	1.66 ± 0.04 ^c	0.76 ± 0.04 ^a

Groups	NF-κB (ng/g tissue)	TNF-α (ng/g tissue)	IL-1β (ng/g tissue)	IL-6 (ng/g tissue)	COX-2 (ng/g tissue)
Control	17.0 ± 0.83 ^a	6.26 ± 0.14 ^a	27.1 ±0.98 ^a	5.59 ± 0.08 ^a	23.9 ± 0.87 ^a
CP (10 mg/kg)	59.5 ± 1.17 ^b	14.4 ± 0.19 ^b	96.3 ±1.94 ^b	17.7 ± 0.45 ^b	68.1 ± 1.17 ^b
CP (10 mg/kg) + CAS (50 mg/kg)	29.6 ± 1.35 ^c	9.43 ± 0.16 ^c	39.8 ± 1.39 ^c	8.75 ± 0.07 ^c	38.1 ± 13.35 ^c
CAS (50 mg/kg)	16.5 ± 0.40 ^a	6.08 ± 0.06 ^a	26.05 ±1.20 ^a	5.54 ± 0.06 ^a	23.6 ± 0.40 ^a

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