Protective effect of melatonin and agomelatine on adriamycin-induced nephrotoxicity in rat model: a renal scintigraphy and biochemical study

Abstract

OBJECTIVE: We aimed to determine the possible protective effects of melatonin and agomelatine on an animal model of adriamycin nephrotoxicity by 99m Tc DMSA renal scintigraphy and biochemical methods. METHODS: Ten weeks old 49 male Wistar rats were randomly separated into seven groups; namely control (CON), adriamycin (ADR), melatonin (MEL), agomelatine (AGO), melatonin + adriamycin (MEL+ADR), agomelatine + adriamycin (AGO+ADR) and melatonin + agomelatine + adriamycin (MEL+AGO+ADR) groups. Nephrotoxicity was induced by a three-dose of 18 mg/kg adriamycin, i.p. at a 24 h interval on the 5th, 6th and 7th days. A dose of melatonin and agomelatine (40 mg/kg/i.p, the same doses) were injected for 7 days before and after the injected of ADR (18 mg/kg, i.p.), respectively. On the 8th day of the experiment, all animals were evaluated and scintigraphic and biochemical parameters were assessed, respectively. RESULTS: ADR signifi cantly increased blood urea nitrogen (1040 %) and plasma creatinine (1020 %), and decreased 99m Tc DMSA uptake levels (59 %) compared to the control (p < 0.001). Pretreatment with MEL, AGO, MEL+AGO mitigated these abnormalities produced by ADR in the kidney (p < 0.001). CONCLUSION: 99m Tc DMSA for the early determination of ADR-induced nephrotoxicity had an important role. Also, a signifi cant correlation was found between biochemical and scintigraphy parameters. Adriamycin caused signifi cant damages to kidneys that were reduced with MEL and AGO (Tab. 2, Fig. 3, Ref. 39).

Evaluation of the protective effect of paricalcitol and vitamin D3at doxorubicin nephrotoxicity in rats with99mTechnetium-dimercaptosuccinic acid renal scintigraphy and biochemical methods

“…40,41 Previous studies demonstrated that DOX injection induces renal injury revealed by higher BUN and creatinine levels. 33,42 –46 Similarly, in the present study, DOX injection increased serum creatinine and BUN levels in rats, which is an indication of nephrotoxicity and a decrease in glomerular filtration. 47…”

Doxorubicin-induced nephrotoxicity model in Wistar rats: Characterization of biochemical parameters, histological and immunohistochemical assessment

“…Similarly, a significant increase in the level of serum urea nitrogen was observed in nephrotoxic rats administered with a single dose of DXR at 20 mg/kg (26%), and 23 mg/kg (41%), when compared to the experimental rats of vehicle group (p<0.05). These elevated concentrations of serum urea nitrogen and creatinine, especially at 20 and 23 mg/kg doses of DXR substantiate the fact that more than 50% of the nephrons are functionally damaged, which denotes severe nephrotoxicity (Perše and Veceric-Haler, 2018;Aygun and Gul, 2019). The findings are consistent with those of the previous reports on DXR-induced nephrotoxicity model (Yilmaz et al, 2006).…”

Protective effect of edaravone on adriamycin-induced cardiotoxicity in rats

“…37 Mbq 99m Tc-PYP radiopharmaceutical was injected i.p. to anesthetized rats 8,9 . One hour after 99m Tc-PYP radiopharmaceutical injection and after ECG recording, static imaging with a dual head gamma camera (E-CAM, Siemens, Germany) was performed in anterior and posterior positions with 2.55 zoom factor.…”

“…In addition, ADR-induced cardiotoxicity is still not yet fully understood, but emerging data implicate the role of production of free radicals and subsequent oxidative stress 4 . ADR-induced oxidative stress has been shown to be inhibited by the treatment of antioxidants in many experimental animals models [5][6][7][8][9] .…”