Publications by authors named "R M Abd-Elsalam"

31 Publications

Novel promising reproductive and metabolic effects of Cicer arietinum L. extract on letrozole induced polycystic ovary syndrome in rat model.

J Ethnopharmacol 2021 Oct 7;278:114318. Epub 2021 Jun 7.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt. Electronic address:

Ethnopharmacological Relevance: Chickpea was used in both greek and indian traditional medicine for hormonal related conditions as menstrual induction, acceleration of parturation, treatment of retained placenta and stimulation of lactation. Chickpea (Cicer arietinum) sprout isoflavone isolates exhibited reasonable estrogenic activities. Isoflavones, a subtype of phytoestrogens, are plant derivatives with moderate estrogenic activity that tend to have protective effects on hormonal and metabolic abnormalities of women with polycystic ovary syndrome (PCOS).

Aim Of The Study: In this study, we investigated the effect of UPLC/ESI-MS characterized Cicer arietinum L. seeds ethanol extract (CSE) on ovarian hormones, oxidative response and ovarian histological changes on induced PCOS rat model.

Materials And Methods: Thirty-five rats were divided into five groups including negative control, PCOS, and treatment groups. PCOS was induced using letrozole (1 mg/kg) daily orally for 21 days. Each treatment group was treated with one of the following for 28 days after induction of PCOS: clomiphene citrate (1 mg/kg), and CSE at 250 and 500 mg/kg. Ovaries and uteri were excised, weighed and their sections were used for quantitative real-time reverse transcriptase polymerase chain reaction, antioxidant assays and histomorphometric study of the ovaries. The antioxidant assays, histopathological examination, hormonal and metabolic profiles, and Cyp11a1(steroidogenic enzyme) mRNA expression were measured.

Results: In all treatment groups, ovarian weight was significantly decreased despite having no significant effect on uterine weight. Histomorphometric study in the treatment groups revealed a significant decrease in the number and diameter of cystic follicles, a significant increase in granulosa cell thickness while, thickness of theca cells was significantly decreased when compared to PCOS. Hormone levels, metabolic profile and antioxidant status were improved in the treatment groups. Moreover, Cyp11a1 mRNA expression was significantly downregulated in the treatment groups compared to PCOS.

Conclusions: In the current study, CSE enhanced the reproductive and metabolic disorders which were associated with PCOS induction. For the first time, we have highlighted the effect of CSE in treating PCOS and its associated manifestations.
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http://dx.doi.org/10.1016/j.jep.2021.114318DOI Listing
October 2021

Linum usitatissimum seeds oil down-regulates mRNA expression for the steroidogenic acute regulatory protein and Cyp11A1 genes, ameliorating letrezole-induced polycystic ovarian syndrome in a rat model.

J Physiol Pharmacol 2021 Feb 3;72(1). Epub 2021 Jun 3.

Department of Physiology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

The safety and effectiveness of nutricetics suggest that they may offer an alternative to pharmaceutical and surgical therapy for hormone-dependent disorders, such as polycystic ovarian syndrome (PCOS). We investigated the effects of Linum usitatissimum seed oil (LSO) on ovarian functionality, its molecular targets, and the oxidative response in hyperandrogenism-induced polycystic ovary. The composition of LSO has been analyzed using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS). A well-established PCOS rat model orally administered with letrozole daily for 21 days was used to investigate the effect of LSO at doses of 1 and 2 mL/kg body weight for 28 days. The effect on hormonal profile and antioxidant status, histopathology (cell proliferation), and the expression ratio of the steroidogenic acute regulatory protein (StAR) and Cyp11A1 gene were evaluated. LSO exerted beneficial effects on PCOS rat models via restoring glutathione (GSH), malondialdehyde (MDA), beta subunit subunit luteinizing hormone (LH), testosterone levels, and histopathological scoring. Furthermore, LSO reversed the elevated StAR and Cyp11A1 genes in the PCOS rat model. This study demonstrated the molecular and cellular mechanisms of the beneficial effect of LSO against the reproductive and metabolic disorders of PCOS.
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http://dx.doi.org/10.26402/jpp.2021.1.06DOI Listing
February 2021

Benzyl isothiocyanates modulate inflammation, oxidative stress, and apoptosis via Nrf2/HO-1 and NF-κB signaling pathways on indomethacin-induced gastric injury in rats.

Food Funct 2021 Jul 26;12(13):6001-6013. Epub 2021 May 26.

Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt.

The present study investigated the gastroprotective activity of benzyl isothiocyanates (BITC) on indomethacin (IND)-induced gastric injury in a rat model and explicated the possible involved biochemical, cellular, and molecular mechanisms. The rat model with gastric ulcers was established by a single oral dose of IND (30 mg per kg b.wt). BITC (0.75 and 1.5 mg kg) and esomeprazole (20 mg per kg b.wt) were orally administered for 3 weeks to rats before the induction of gastric injury. Compared with the IND group, BITC could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. BITC significantly preserved the antioxidants (glutathione GSH, superoxide dismutase SOD), nitric oxide (NO), and prostaglandin E2 (PGE2) contents, while decreasing the gastric mucosal malondialdehyde (MDA), tumor necrosis factor alpha (TNFα), and myeloperoxidase (MPO) contents. Moreover, BITC remarkably upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), hemoxygenase-1 (HO-1), and NAD(P)H : quinone oxidoreductase (NQO1). In addition, BITC activates the expression of heat shock protein 70 (HSP-70) and downregulated the expression of nuclear factor-κB (NF-κB) and caspase-3 to promote gastric mucosal cell survival. To the best of our knowledge, this study is the first published report to implicate the suppression of inflammation, oxidative stress, and Nrf2 signaling pathway as a potential mechanism for the gastroprotective activity of BITC.
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http://dx.doi.org/10.1039/d1fo00645bDOI Listing
July 2021

Eruca sativa seed extract modulates oxidative stress and apoptosis and up-regulates the expression of Bcl-2 and Bax genes in acrylamide-induced testicular dysfunction in rats.

Environ Sci Pollut Res Int 2021 May 23. Epub 2021 May 23.

Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.

Acrylamide (ACR) has been previously associated with male sexual dysfunction and infertility. Eruca sativa (L.) (arugula or rocket) have been widely used in traditional remedies in Mediterranean region and western Asia and was known for its strong aphrodisiac effect since Roman times. The current study was designed to investigate LC/MS analysis of total ethanol extract Eruca sativa (L.) and the efficiency and mechanism of action of Eruca sativa seed extract (ESS) in reducing hypogonadism induced by acrylamide in male rats. Male Wistar rats were divided into 6 groups (n = 7): control group, Eruca sativa seed extract (ESS) at doses of 100 and 200 mg\kg, acrylamide (ACR), ACR + ESS 100 mg/kg, and ACR + ESS 200 mg/kg. The animals received ACR at a dose of 10 mg/kg b.wt for 60 days. Sperm indices, testicular oxidative stress, testosterone hormone, and testicular histopathology and immunohistochemistry of PCNA and caspase-3 were investigated. Moreover, the expression level of testicular B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) genes was evaluated. In respect to the LC/MS of total ethanol extract Eruca sativa (L.) seed revealed tentative identification of 39 compounds, which belongs to different classes as sulphur-containing compounds, flavonoids, phenolic acid, and fatty acids. Administration of ESS extract (100, 200 mg/kg) improved semen quality, diminished lipid peroxidation, enhanced testicular antioxidant enzyme, restored serum testosterone level, and reduced testicular degeneration and Leydig cell death in the rats intoxicated with ACR. However, the effects of ESS at the dose of 200 mg/kg were similar to that of control group. Furthermore, ESS treatment significantly induced anti-apoptotic effect indicated by elevation of both Bcl-2 and Bax expressions. Nutriceutics of ESS extract protects testis against ACR-induced testicular toxicity via normalizing testicular steroidogenesis, keeping Leydig cells, and improving oxidative stress status.
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http://dx.doi.org/10.1007/s11356-021-14532-yDOI Listing
May 2021

Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: promising activity without the risk of hepatic adverse effect.

Chin Med 2021 Apr 29;16(1):36. Epub 2021 Apr 29.

Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt.

Background: Complementary remedies such as the Chinese herb 'Sheng Ma' (Black cohosh; Actaea racemosa 'AR') are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for the treatment of polycystic ovary syndrome (PCOS). However, AR-induced hepatotoxicity necessitates a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products.

Methods: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed. The rats then received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, holistic profiling of the AR arsenal of secondary metabolites was performed using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole high-resolution time of flight mass spectrometry (QTOF-MS).

Results: Beneficial effects were exerted by AR in PCOS rats as antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells were all improved. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic malondialdehyde (MDA) and glutathione (GSH) levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes.

Conclusion: This study demonstrated the benefit of the combinatorial effects of AR and vitamin C in mitigating the reproductive and metabolic disorders associated with PCOS with the elimination of AR hepatotoxic risk.
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http://dx.doi.org/10.1186/s13020-021-00444-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086310PMC
April 2021