Protective effects of lemon and orange peels and olive oil on doxorubicin-induced myocardial damage via inhibition of oxidative stress and inflammation pathways Amal I. El-Refaiy, Zainab A. Salem, Abdelnaser A. Badawy, Naief Dahran, Muhammad A. Desouky, et al. Frontiers in Pharmacology, 2025 Background/aimCompounds originating from plants, especially citrus fruits and olive oil, have anti-inflammatory, cardioprotective, and antioxidant characteristics. Doxorubicin (DOX), an anthracycline antineoplastic, induces cardiotoxicity by generating free radicals. This study aimed to evaluate the cardioprotective effects of orange (OP) and lemon (LP) peels and olive oil (OO) against DOX-induced myocardial damage in rats.MethodsThirty adult male albino rats were randomly assigned to five groups, with six rats in each group. The control group was labeled Group I (Cnt), while Group II (DOX) got DOX intraperitoneally. Groups III, IV, and V were given a combination of DOX with OP, LP, or OO, respectively. After 28 days, cardiac biomarkers (AST, LDH, CK, cTnT), oxidative stress markers (NO, MDA), antioxidant enzyme activities (SOD, CAT, GPx), apoptotic genes (Bax, caspase 3, Bcl2), NFκB and inflammatory cytokines (TNFα, IL1β) were assessed. Histopathological analysis of the heart was also conducted.ResultsDOX-treated rats showed significant functional and structural cardiac damage, characterized by elevated AST, LDH, CK, cTnT, NO, MDA, Bax, caspase 3, NFκB, TNFα, IL1β and reduced SOD, CAT, GPx, and Bcl2 levels. These rats exhibited myocardial necrosis, inflammatory infiltration, mitochondrial damage, and myofibril atrophy. Treatment with OP, LP, or OO mitigated these effects, with OO providing the most substantial protection.ConclusionThese findings suggest that OP, LP, or OO can reduce DOX-induced cardiac toxicity by decreasing oxidative stress, apoptosis, and inflammation.
Unraveling the Nephroprotective Potential of Papaverine against Cisplatin Toxicity through Mitigating Oxidative Stress and Inflammation: Insights from In Silico, In Vitro, and In Vivo Investigations Shimaa A. Abass, Abdullah A. Elgazar, Sanad S. El-kholy, Amal I. El-Refaiy, Reem A. Nawaya, et al. Molecules Basel Switzerland, 2024 Cisplatin is a potent compound in anti-tumor chemotherapy; however, its clinical utility is hampered by dose-limiting nephrotoxicity. This study investigated whether papaverine could mitigate cisplatin-induced kidney damage while preserving its chemotherapeutic efficacy. Integrative bioinformatics analysis predicted papaverine modulation of the mechanistic pathways related to cisplatin renal toxicity; notably, mitogen-activated protein kinase 1 (MAPK1) signaling. We validated protective effects in normal kidney cells without interfering with cisplatin cytotoxicity on a cancer cell line. Concurrent in vivo administration of papaverine alongside cisplatin in rats prevented elevations in nephrotoxicity markers, including serum creatinine, blood urea nitrogen, and renal oxidative stress markers (malondialdehyde, inducible nitric oxide synthase (iNOS), and pro-inflammatory cytokines), as tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and interleukin-6 (IL-6). Papaverine also reduced apoptosis markers such as Bcl2 and Bcl-2–associated X protein (Bax) and kidney injury molecule-1 (KIM-1), and histological damage. In addition, it upregulates antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) while boosting anti-inflammatory signaling interleukin-10 (IL-10). These effects were underlined by the ability of Papaverine to downregulate MAPK-1 expression. Overall, these findings show papaverine could protect against cisplatin kidney damage without reducing its cytotoxic activity. Further research would allow the transition of these results to clinical practice.
Anticryptosporidium efficacy of olea europaea and ficus carica leaves extract in immunocompromised mice associated with biochemical characters and antioxidative system Wafaa Fayez Abd El-Hamed, Nahed Samy Yousef, Yasser S. A. Mazrou, Walaa A. E. S. Elkholy, Amal I. El-Refaiy, et al. Cells, 2021 Cryptosporidiosis is caused by an opportunistic protozoan parasite (Cryptosporidium parvum and C. hominis) known as a parasite of humans, especially children and immunocompromised patients. The current study was designed to evaluate the therapeutic efficacy of a mixture of fig and olive leaf extracts as an alternative medicinal plant. Parasitological examination for oocysts in the stool and histopathological alterations in the small intestines were examined. Additionally, biochemical analyses of liver and kidney functions in addition to antioxidant parameters such as superoxide dismutase (SOD), glutathione peroxidase (GSH) and catalase (CAT) in the plasma were evaluated. Our results showed that marked reduction in oocysts shedding and amelioration in intestinal histopathological changes and hepatic or renal functions were detected in all treated groups compared to the control infected group. Additionally, the treated groups with tested extracts at ratios 1:3 and 1:5 showed a significant decrease in the number of oocysts compared to the other treated groups. Results exhibited a significant increase in the plasma SOD, CAT and GSH levels in treated groups compared to the infected control one. This study suggested that a mixture of fig and olive leaf extracts is a convenient promising therapeutic agent for Cryptosporidiosis.
Immobilization stress- related alterations in ultrastructure of skeletal muscle of albino rat and the role of diazepam Research Journal of Pharmaceutical Biological and Chemical Sciences, 2014
Effect of immobilization stress on the cytoskeletal intermediate filaments of rat stomach and the possible curative role of diazepam Life Science Journal, 2013
Protective effects of ascorbic acid and zinc against cadmium-induced histopathological, histochemical and cytogenetic changes in rats Comunicata Scientiae, 2012
RECENT SCHOLAR PUBLICATIONS
Magnetized water mitigates AlCl3-induced oxidative stress and Alzheimer's-like neurotoxicity in rats SFM Dawoud, SA El-Shazly, AI El-Refaiy, HI Ghamry, AM Sharaf-Eldin, ... Journal of Radiation Research and Applied Sciences 18 (3), 101660 , 2025 2025 Citations: 2
Impact of dandelion (Taraxacum officinale) leaf aqueous extract on immunological response of mice after Schistosoma mansoni infection AI El-Refaiy, NS Amer, A Alhejely, SH Qahl, AM Shaban, AE Mohamed, ... Molecular and Biochemical Parasitology 262, 111673 , 2025 2025 Citations: 5
Protective effects of lemon and orange peels and olive oil on doxorubicin-induced myocardial damage via inhibition of oxidative stress and inflammation pathways AI El-Refaiy, ZA Salem, AA Badawy, N Dahran, MA Desouky, MA El-Magd Frontiers in Pharmacology 16, 1506673 , 2025 2025 Citations: 8
Unraveling the nephroprotective potential of papaverine against cisplatin toxicity through mitigating oxidative stress and inflammation: insights from in silico, in vitro, and … SA Abass, AA Elgazar, SS El-Kholy, AI El-Refaiy, RA Nawaya, MA Bhat, ... Molecules 29 (9), 1927 , 2024 2024 Citations: 27
Ameliorative Effect of Dandelion Leaves Extract Against Liver Injury Induced by Schistosomiasis in Mice NS Amer, AI El-Refaiy Journal of Pharmaceutical Negative Results, 2554-2569 , 2022 2022 Citations: 5
Anticryptosporidium Efficacy of Olea europaea and Ficus carica Leaves Extract in Immunocompromised Mice Associated with Biochemical Characters and … WF Abd El-Hamed, NS Yousef, YSA Mazrou, WAES Elkholy, AI El-Refaiy, ... Cells 10 (9), 2419 , 2021 2021 Citations: 21
Short Term Effects of Dexamethasone on Histological Structure of Adrenal Gland and Testis of Male Mouse AI El-Refaiy Current Science International 8 (4), 838-845 , 2019 2019
Changes in the Cytoskeletal Intermediate Filaments of Testicular Tissues of Rabbits Related with Age and the Prophylactic Role of Vitamin E NIE Desouki1, AI El-Refaiy2, DF Afifi1, H Talaat1 International Journal of Scientific & Engineering Research 8 (6), 260-271 , 2017 2017
Cytogenetical study on the Effect of Immobilization Stress on Albino Rat and the Ameliorative Role of Diazepam HAAMME Amal I. El-Refaiy1,2, Nabila I. El-Desouki3 Current Science International , 2017 2017 Citations: 2
Histological study on the effect of meloxicam on cardiac muscles and gastric mucosa in adult male albino rats EHEAI El-Refaiy Middle East Journal of Applied Science 6 (2) , 2017 2017
Age-Related Changes in the Histological Structure of Rabbit Testes and the Prophylactic Role of Vitamin E NI El-Desouki, AI El-Refaiy, DF Afifi, H Talaat Journal of Bioscience and Applied Research 2 (5), 312-318 , 2016 2016 Citations: 1
Age-related changes in histological and cytoskeletal intermediate filaments of rabbits thyroid glands and the prophylactic role of vitamin E NI El-Desouki, DF Afifi, AI El-Refaiy, H Talaat Glob Vet 13 (13), 511-519 , 2014 2014 Citations: 6
Immobilization Stress- Related alterations in Ultrastructure of Skeletal Muscle of Albino Rat and the Role of Diazepam. AIERAAAK Nabila I El-Desouki , Dalia F Afifi Research Journal of Pharmaceutical, Biological and Chemical Sciences 5 (4 … , 2014 2014 Citations: 2
Histopathology and cytotoxicity as biomarkers in treated rats with cadmium and some therapeutic agents AI El-Refaiy, FI Eissa Saudi journal of biological sciences 20 (3), 265-280 , 2013 2013 Citations: 131
Effect of immobilization stress on the cytoskeletal intermediate filaments of rat stomach and the possible curative role of diazepam NI El–Desouki, AI El-Refaiy, GM Sayed, MA Ibrahim, HN Mohamed Life Sci J Assist Repred Genet 2 (3), 10 , 2013 2013 Citations: 3
Protective effects of ascorbic acid and zinc against cadmium-induced histopathological, histochemical and cytogenetic changes in rats AI El-Refaiy, F Eissa Comunicata Scientiae 3 (3), 162-180 , 2012 2012 Citations: 52
ANTIMUTAGENIC EFFECTS OF CHITOSAN AGAINST THE CY-TOLOGICAL AND BIOCHEMICAL CHANGES INDUCED BY AFLATOXINS IN RATS GAB EL-FADLY, OLAA GALAL, AA EL-REFAIY, AA MUSTAFA, ... Egyptian Journal of Genetics And Cytology 41 (1) , 2012 2012
Histological, histochemical, and immunohistochemical studies of the cardiac muscle of the albino rat under immobilization stress and the curative role of diazepam NI El-Desouki, AI El-Refaiy, DF Afifi, AA Abdel-Kader The Egyptian Journal of Experimental Biology (Zoology) 8 (2), 273-285 , 2012 2012 Citations: 14
COMPARATIVE STUDIES OF THE PANCREAS OF TWO SPECIES OF DOVE, STREPTOPELIA ROSEOGRISAE AND STREPTOPELIA SENEGALENSIS AI El-Refaiy, DFA Abou-Zaid, NI El-Desouki THE EGYPTIAN JOURNAL OF EXPERIMENTAL BIOLOGY (Zoology) 7 (2), 313-313 , 2011 2011
HISTOLOGICAL STUDY ON THE STOMACH OF IMMOBILIZED - STRESSED ALBINO RAT AND THE CURATIVE ROLE OF DIAZEPAM GMSEDNIERAIIMAEMH Nagy* Egypt. J. Exp. Biol. (Zool.), 7 (2), 153-161 , 2011 2011 Citations: 6
MOST CITED SCHOLAR PUBLICATIONS
Histopathology and cytotoxicity as biomarkers in treated rats with cadmium and some therapeutic agents AI El-Refaiy, FI Eissa Saudi journal of biological sciences 20 (3), 265-280 , 2013 2013 Citations: 131
Protective effects of ascorbic acid and zinc against cadmium-induced histopathological, histochemical and cytogenetic changes in rats AI El-Refaiy, F Eissa Comunicata Scientiae 3 (3), 162-180 , 2012 2012 Citations: 52
Unraveling the nephroprotective potential of papaverine against cisplatin toxicity through mitigating oxidative stress and inflammation: insights from in silico, in vitro, and … SA Abass, AA Elgazar, SS El-Kholy, AI El-Refaiy, RA Nawaya, MA Bhat, ... Molecules 29 (9), 1927 , 2024 2024 Citations: 27
Anticryptosporidium Efficacy of Olea europaea and Ficus carica Leaves Extract in Immunocompromised Mice Associated with Biochemical Characters and … WF Abd El-Hamed, NS Yousef, YSA Mazrou, WAES Elkholy, AI El-Refaiy, ... Cells 10 (9), 2419 , 2021 2021 Citations: 21
Histological, histochemical, and immunohistochemical studies of the cardiac muscle of the albino rat under immobilization stress and the curative role of diazepam NI El-Desouki, AI El-Refaiy, DF Afifi, AA Abdel-Kader The Egyptian Journal of Experimental Biology (Zoology) 8 (2), 273-285 , 2012 2012 Citations: 14
Histological and histochemical studies on the testes of albino rat under immobilization stress and the possible curative role of diazepam AI El-Refaiy J Egypt Ger Soc Zool 60, 1-22 , 2010 2010 Citations: 10
Protective effects of lemon and orange peels and olive oil on doxorubicin-induced myocardial damage via inhibition of oxidative stress and inflammation pathways AI El-Refaiy, ZA Salem, AA Badawy, N Dahran, MA Desouky, MA El-Magd Frontiers in Pharmacology 16, 1506673 , 2025 2025 Citations: 8
Histological and ultrasructural studies of the effect of immobilization stress on the adrenal cortex of albino rat and the ameliorative role of diazepam N El-Desouki, A El-Refaiy, H Abdel-Azeem, M El-Baely J. Egypt. Ger. Soc. Zool 62, 25-45 , 2011 2011 Citations: 8
Age-related changes in histological and cytoskeletal intermediate filaments of rabbits thyroid glands and the prophylactic role of vitamin E NI El-Desouki, DF Afifi, AI El-Refaiy, H Talaat Glob Vet 13 (13), 511-519 , 2014 2014 Citations: 6
HISTOLOGICAL STUDY ON THE STOMACH OF IMMOBILIZED - STRESSED ALBINO RAT AND THE CURATIVE ROLE OF DIAZEPAM GMSEDNIERAIIMAEMH Nagy* Egypt. J. Exp. Biol. (Zool.), 7 (2), 153-161 , 2011 2011 Citations: 6
Biochemical and histological studies on the Ameliorative role of fenugreek products in tannic acid-induced iron deficiency anemia in Albino rats ERA Ibrahim, MN Yehia Egypt. J. Exp. Biol 7, 185-196 , 2011 2011 Citations: 6
Impact of dandelion (Taraxacum officinale) leaf aqueous extract on immunological response of mice after Schistosoma mansoni infection AI El-Refaiy, NS Amer, A Alhejely, SH Qahl, AM Shaban, AE Mohamed, ... Molecular and Biochemical Parasitology 262, 111673 , 2025 2025 Citations: 5
Ameliorative Effect of Dandelion Leaves Extract Against Liver Injury Induced by Schistosomiasis in Mice NS Amer, AI El-Refaiy Journal of Pharmaceutical Negative Results, 2554-2569 , 2022 2022 Citations: 5
Effect of immobilization stress on the cytoskeletal intermediate filaments of rat stomach and the possible curative role of diazepam NI El–Desouki, AI El-Refaiy, GM Sayed, MA Ibrahim, HN Mohamed Life Sci J Assist Repred Genet 2 (3), 10 , 2013 2013 Citations: 3
A study on some lymphoid organs of two common species of bats from Egypt, Rousettus aegypticus and Taphozous nudiventris WY Attia, N El‐Desouki, GA Madkour, AEI Sayed, A El‐Refaiy Egyptian Journal of Experimental Biology (Zoology) 3, 151-161 , 2007 2007 Citations: 3
Histological, cytological and histochemical studies on the stomach of two common species of Egyptian bats, Rousettus aegyptiacus and Taphozous nudiventris NI El-Desouki, G Madkour, AEH Sayed, WY Attia, AI El-Refaiy Egyptian Journal of Experimental Biology (Zoology) 152, 137-152 , 2006 2006 Citations: 3
Magnetized water mitigates AlCl3-induced oxidative stress and Alzheimer's-like neurotoxicity in rats SFM Dawoud, SA El-Shazly, AI El-Refaiy, HI Ghamry, AM Sharaf-Eldin, ... Journal of Radiation Research and Applied Sciences 18 (3), 101660 , 2025 2025 Citations: 2
Cytogenetical study on the Effect of Immobilization Stress on Albino Rat and the Ameliorative Role of Diazepam HAAMME Amal I. El-Refaiy1,2, Nabila I. El-Desouki3 Current Science International , 2017 2017 Citations: 2
Immobilization Stress- Related alterations in Ultrastructure of Skeletal Muscle of Albino Rat and the Role of Diazepam. AIERAAAK Nabila I El-Desouki , Dalia F Afifi Research Journal of Pharmaceutical, Biological and Chemical Sciences 5 (4 … , 2014 2014 Citations: 2
Age-Related Changes in the Histological Structure of Rabbit Testes and the Prophylactic Role of Vitamin E NI El-Desouki, AI El-Refaiy, DF Afifi, H Talaat Journal of Bioscience and Applied Research 2 (5), 312-318 , 2016 2016 Citations: 1