Renal Protective effects of Melatonin in rat treat by Gemcitabine

Mortazavi, Pejman; Ahmadnezhad, Behnam; Pousty, I; Panahi, Negar; Aghazadeh, Mitra; Shalikar, Mostafa; Ramezani, Vahid; Meybodi, Maryam Aghaie

doi:10.17352/ijvsr.000025

Cited by 3 publications

(7 citation statements)

References 16 publications

(16 reference statements)

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“…The results of this study were also in agreement with Mortazavi et al [16] results who studied the effect of melatonin on protecting the renal tissue in rats treated by single high dose of gemcitabine and found some remarkable little pathological changes in renal tissue.…”

Section: Group Csupporting

confidence: 93%

“…Renal sections of this group showed various pathological changes including severe degeneration and necrosis of the renal tubules, thickening of blood vessel wall with thrombus formation, mononuclear inflammatory cells infiltration with cyst formation in the interstitial tissue, lobulation of glomeruli, and expansion of Bowman's space with hyaline cast formation in the renal tubules. These results were in agreement with Mortazavi et al [16] study who noticed that gemcitabine treated rat group suffered from severe renal tissue damage including degeneration and necrosis of renal tubules with inflammatory cells infiltration in interstitium of kidney.…”

Section: Histological Examinationsupporting

confidence: 93%

“…Group C received gemcitabine intraperitoneally in a dose of 25 mg/kg and melatonin orally in a dose of 10mg/kg once per week for 4 successive weeks. Group D received only melatonin 10mg/kg once per week for 4 weeks [16], [17].…”

Section: Experimental Designmentioning

confidence: 99%

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Histological Effect of Gemcitabine on the Liver and Kidney of Male Rat with and without Melatonin

Abdullah

Ismail

AL-Hubaity

2022

Open Access Maced J Med Sci

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Background: the aim of this study is to identify the toxic effect of gemcitabine on the kidney and liver tissues of rat and whether melatonin has any protective effect on these tissues. MATERIALS AND METHODS: 32 adults male Wistar rats were selected and divided into four groups. Group A was the control group that received normal saline. Group B received gemcitabine alone in a dose of 25mg/kg body weight intraperitoneally once per week for four successive weeks. Group C received gemcitabine intraperitoneally in a dose of 25mg/ kg and melatonin orally in a dose of 10mg/kg once per week for four successive weeks. Group D received only melatonin 10mg/kg once per week for four weeks. RESULTS: The histological changes of liver of group B showed disorganization of hepatic tissue with congestion in the portal area and chronic inflammatory cells infiltration in the periportal area. Nuclei of some hepatocytes were vesicular with steatosis. In group C liver sections showed inflammatory cell infiltration with mild pyknosis of some hepatocytes. Liver sections of group D were limited to degeneration of some hepatocyte. Renal sections of group B showed degeneration and necrosis of epithelial cells with thickening of blood vessel wall, congestion and thrombus formation with cystic appearance in the interstitial tissue were detected. While in group C the histological sections showed swelling of epithelial cells lining renal tubules with congestion of blood vessels. Renal sections of group D were more or less normal. CONCLUSION: the present study concluded that gemcitabine induced toxic effect on liver and kidney of male rats and melatonin may play protective effect on the tissue of these organs. Key wards: gemcitabine, melatonin, liver, kidney, rat

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Section: Group Csupporting

confidence: 93%

Section: Histological Examinationsupporting

confidence: 93%

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Histological Effect of Gemcitabine on the Liver and Kidney of Male Rat with and without Melatonin

Abdullah

Ismail

AL-Hubaity

2022

Open Access Maced J Med Sci

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“…Melatonin 10 mg capsules (Puritan’s Pride) 20 mg/kg were given daily by oral gavage ( Mortazavi et al, 2017 ; Aygun and Gul, 2019 ). Melatonin was prepared by adding Tween 80 at a concentration of 10 mg/ml ( Elshall et al, 2022 ) and then distilled water ( Shokrzadeh et al, 2014 ; Mahmoud and El-Deek, 2019 ) at a concentration of 2.4 mg/ml ( Supplementary Figure S9 ).…”

Section: Methodsmentioning

confidence: 99%

Synergistic cardioprotective effects of melatonin and deferoxamine through the improvement of ferritinophagy in doxorubicin-induced acute cardiotoxicity

et al. 2022

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Ferritinophagy is one of the most recent molecular mechanisms affecting cardiac function. In addition, it is one of the pathways by which doxorubicin, one of the anticancer drugs commonly used, negatively impacts the cardiac muscle, leading to cardiac function impairment. This side effect limits the use of doxorubicin. Iron chelators play an important role in hindering ferritinophagy. Antioxidants can also impact ferritinophagy by improving oxidative stress. In this study, it was assumed that the antioxidant function of melatonin could promote the action of deferoxamine, an iron chelator, at the level of ferritinophagy. A total of 42 male Wistar rats (150–200 g) were divided into seven groups (n = 6) which consisted of group I: control normal, group II: doxorubicin (Dox), group III: melatonin (Mel), group IV: deferoxamine (Des), group V: Mel + Dox, group VI: Des + Dox, and group VII: Mel + Des + Dox. Groups III, V and VII were orally pretreated with melatonin 20 mg/kg/day for 7 days. Groups IV, VI and VII were treated with deferoxamine at a 250 mg/kg/dose once on D4 before Dox was given. Doxorubicin was given at a 20 mg/kg ip single dose. On the 8th day, the rats were lightly anaesthetized for electrocardiography analysis and echocardiography. Serum samples were collected and then sacrificed for tissue sampling. The following biochemical assessments were carried out: PCR of NCOA4, IREB2, FTH1, SLC7A11, and GPX4; and ELISA for serum cTnI, serum transferrin, tissue GSH, and malondialdehyde. In addition, histopathological assessment of heart injury; immunostaining of caspase-3, Bax, and Bcl2; and physiological function assessment by ECG and ECHO were carried out. Doxorubicin-induced acute significant cardiac injury with increased ferritinophagy and apoptosis responded to single and combined prophylactic treatment, in which the combined treatment showed mostly the best results. In conclusion, using melatonin as an antioxidant with an iron chelator, deferoxamine, could hinder the hazardous cardiotoxic effect of doxorubicin. However, further studies are needed to detect the impact of higher doses of melatonin and deferoxamine with a prolonged treatment period.

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“…The maximum concentration for gemcitabine is 40 mg/kg. In this study, we used a concentration of 20 mg/kg [8].…”

Section: Preparation Of Gamcitabinementioning

confidence: 99%

Evaluation of the protective effect of melatonin on histological changes in the liver of adult male rats treated with gemcitabine

Khakshour¹,

Ahmadnezhad²,

Shalikar³

et al. 2022

GSC Biol. and Pharm. Sci.

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Melatonin is an endocrine hormone, produced by the pineal gland from the amino acid tryptophan. Melatonin level in the body according to a predetermined cycle and are affected by light received. Gemcitabine is an anti-cancer drug. The mechanism of action of gemcitabine affects the properties of the cellular phase and mainly destroys the cells that are making DNA (phase-s). Nephrotoxic side effects of gemcitabine have been reported in patients receiving this drug medication. Melatonin is a potent free radical scavenger and antioxidant and has protective effects against ischemic damage. The aim of the present study was to investigate the protective effect of melatonin on histological changes in the liver of adult male rats treated with gemcitabine and to evaluate the effects of different doses of melatonin on the protection of adult liver cells treated with gemcitabine. This experimental study was performed on male Wistar rats weighing approximately 250±20g and aged 8 weeks. Mice were randomly divided into 3 main groups. The first group (G1); the control group, received only normal saline. The second group (G2); the treated groups, divided into 2 subgroups T1 and T2, This group received melatonin at doses of 10 and 20 mg/kg and intraperitoneal (IP) with gemcitabine at a dose of 50 mg/kg, respectively. The third group (G3); negative control group, divided into 3 subgroups T3, T4 and T5. Subgroup T3, gemcitabine at 50 mg/kg, and T4 and T5, they received melatonin at doses of 10 and 20 mg/kg, intraperitoneally (IP) respectively. The number of mice in each group was 6 mice. The results obtained from the injection of gemcitabine in groups clearly showed the side and cytotoxic effects in the liver tissue that the most lesions were observed in the subgroup (T3). In the groups receiving melatonin, the amount of these lesions was significantly reduced and the reduction of injuries was directly related to the dose of melatonin. The results of this study show that melatonin is effective in reducing the side effects of gemcitabine.

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Renal Protective effects of Melatonin in rat treat by Gemcitabine

Cited by 3 publications

References 16 publications

Histological Effect of Gemcitabine on the Liver and Kidney of Male Rat with and without Melatonin

Histological Effect of Gemcitabine on the Liver and Kidney of Male Rat with and without Melatonin

Synergistic cardioprotective effects of melatonin and deferoxamine through the improvement of ferritinophagy in doxorubicin-induced acute cardiotoxicity

Evaluation of the protective effect of melatonin on histological changes in the liver of adult male rats treated with gemcitabine

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