Abstract
Simple SummaryThe present study aimed to investigate the protective effect of argan oil against nephrotoxic effect following overdose and long-term administration of betamethasone. The results revealed that betamethasone induced hematological changes, including reduction of red blood cells with leukocytosis, neutrophilia, monocytosis, lymphocytopenia, and marked thrombocytopenia. Moreover, betamethasone caused significant increase of serum urea and creatinine levels; renal malondialdehyde and nitric oxide contents associated with significant decrease of reduced glutathione content. Betamethasone also caused vascular, degenerative, and inflammatory histopathological alterations in kidney tissue along with increase of Bax and caspase-3 expressions and decrease of B-cell lymphoma-2 (Bcl-2) and proliferating cell nuclear antigen (PCNA) expressions. Conversely, the concomitant administration of argan oil (0.5, 1 mL/kg) with betamethasone ameliorated the aforementioned hematological, biochemical, pathological, and histochemical adverse effects. In conclusion, overdose and long-term administration of betamethasone could induce hematological changes and severe renal damage mediated by oxidative, apoptotic and proliferative mechanisms via increasing renal functions biomarkers and altering oxidant/antioxidant status along with pathological lesions and imbalance of Bax/Bcl-2 ratio that positively correlates with up-regulation of caspase-3 and down-regulation of PCNA in kidney tissue. However, argan oil could potentially protect against betamethasone- induced renal damage, in a dose-dependent manner, via its antioxidant, anti-apoptotic and proliferative properties.The present study aimed to investigate the protective effect of argan oil (AO) against nephrotoxic effects following overdose and long-term administration of betamethasone (BM). The phytochemical compositions of AO were assessed using GC/MS. Forty eight male Wister albino rats were divided into six groups and treated for 3 successive weeks. The control group was orally administrated distilled water daily, the BM group received BM (1 mg/kg, IM, day after day), AO/0.5 and AO/1 groups received AO (0.5 mL/kg, 1 mL/kg, orally, daily, respectively), BM + AO/0.5 group and BM + AO/1 group. The results revealed that BM induced hematological changes, including reduction of red blood cells with leukocytosis, neutrophilia, monocytosis, lymphocytopenia, and thrombocytopenia. Moreover, BM caused a significant increase of serum urea and creatinine levels, and renal malondialdehyde and nitric oxide contents with significant decrease of reduced glutathione content. BM also caused vascular, degenerative, and inflammatory histopathological alterations in kidney, along with an increase in the Bax/Bcl-2 ratio, activation of caspase-3, and decrease of proliferating cell nuclear antigen expression. Conversely, the concomitant administration of AO (0.5, 1 mL/kg) with BM ameliorated the aforementioned hematological, biochemical, pathological, and histochemical BM adverse effects. In conclusion, AO has protective effects against BM-induced renal damage, possibly via its antioxidant, anti-apoptotic, and proliferative properties.
Highlights
Glucocorticoids (GCs), a major class of adrenal steroid hormones, are the most important mediators of systemic inflammation and play an essential role in the maintenance of a variety of metabolic and homeostatic functions [1,2]
The immune-staining method for localization of Bax (Bcl-2-associated X), B-cell lymphoma-2 (Bcl-2), and caspase-3 was performed following the method adopted by Hassanein et al [27] and following the method adopted by Zhu et al [28] for localization of proliferating cell nuclear antigen (PCNA)
The results of the phytochemical analysis of Argan oil (AO) using Gas Chromatography–Mass Spectrometry (GC–MS) can be seen in Table 1, which shows the presence of fifteen phyto-constituents, with cyclopentasiloxane, decamethyl, and phenol, 2,6-bis(1,1-dimethylethyl)-4-methyl being the main constituents
Summary
Glucocorticoids (GCs), a major class of adrenal steroid hormones, are the most important mediators of systemic inflammation and play an essential role in the maintenance of a variety of metabolic and homeostatic functions [1,2]. The clinical and therapeutic benefits of synthetic glucocorticoids are associated with many adverse side effects, during high-dose and/or long-term administration [5] Among these adverse effects, neuropsychiatric disorders, hyperglycemia, hypertension, obesity, gastritis, osteoporosis, glaucoma, cataracts, and cardiovascular disease were recorded following exposure to synthetic glucocorticoids [6,7,8,9,10]. Previous literature confirmed the antioxidant, anti-inflammatory, anti-mutagenic, and anti-carcinogenic activities of AO [19,20], as well as its neuroand hepatorenal protective effects [19,21,22] In this context, the current study was designed firstly to investigate the effect of overdose and long-term administration of betamethasone on kidney of rats and the prospective ameliorative effect of argan oil, and to clarify the mechanistic role of oxidative stress, highlighting the relevance between the Bax/Bcl-2 ratio, caspase-3 activity, and apoptosis, as well as renal proliferation
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