Kassab, R. B., A. A. Elhenawy, A. A. Elhenawy, Y. M. Hawsawi, O. M. Al-Amer, A. A. A. Oyouni, O. A. Habotta, H. A. Althagafi, F. Alharthi, M. S. Lokman, et al., "Modulation of inflammatory, oxidative, and apoptotic stresses mediates the renoprotective effect of daidzein against glycerol-induced acute kidney injury in rats.", Environmental science and pollution research international, vol. 30, issue 56, pp. 119016-119033, 2023. Abstractmodulation_of_inflammatory_oxidative_and_apoptotic_stresses_mediates_the_renoprotective_effect_of_daidzein_against_glycerol-induced_acute_kidney_injury_in_rats.pdf

Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities. This study examined the therapeutic potential of daidzein and the underlying mechanisms against AKI induced by glycerol in male rats. Animals were injected once with glycerol (50%, 10 ml/kg, intramuscular) for induction of AKI and pre-treated orally with daidzein (25, 50, and 100 mg/kg) for 2 weeks. Biochemical, histopathological, immunohistopathological, and molecular parameters were assessed to evaluate the effect of daidzein. The results revealed that the model group displayed remarkable functional, molecular, and structural changes in the kidney. However, pre-administration of daidzein markedly decreased the kidney relative weight as well as the levels of urea, creatinine, K, P, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C. Further, daidzein lessened the rhabdomyolysis-related markers [lactate dehydrogenase (LDH) and creatine kinase (CK)]. Notably, the enhancement of the antioxidant biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione (GSH) is accompanied by a decrease in malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, upregulated gene expression levels of nuclear factor erythroid 2-related factor 2 (Nfe212) and hemeoxygenase-1 (Hmox1) were exerted by daidzein administration. Rats who received daidzein displayed markedly lower interleukin-1β (IL-1β), tumor nuclear factor-α (TNF-α), myleoperoxidase (MPO), and nuclear factor kappa B (NF-κB) levels together with higher interleukin-10 (IL-10) related to the model group. Remarkably, significant declines were noticed in the pro-apoptotic (Bax and caspase-3) and rises in antiapoptotic (Bcl-2) levels in the group that received daidzein. The renal histological screening validated the aforementioned biochemical and molecular alterations. Our findings support daidzein as a potential therapeutic approach against AKI-induced renal injury via suppression of muscle degradation, oxidative damage, cytokine release, and apoptosis.

Almasary, M., K. M. Alkhalifah, S. H. Alotaibi, M. Elhefny, H. Alabssi, S. S. Alaklabi, R. S. Alayed, A. A. Alghamdi, and A. Albalawi, "Prevalence of Irritable Bowel Syndrome in Saudi Arabia: A Systematic Review and Meta-Analysis.", Cureus, vol. 15, issue 9, pp. e45357, 2023. Abstractprevalence_of_irritable_bowel_syndrome_in_saudi_arabia-_a_systematic_review_and_meta-analysis.pdf

Irritable bowel syndrome (IBS) is a commonly found global functional pathology with no detectable structural changes. It affects the quality of life and often coexists with psychiatric and somatic issues. We reviewed all articles published between 1990 and April 2023. The databases used for the data search were Google Scholar, Web of Science, Cochrane Library, and PubMed/MEDLINE. Ovid search engine was also used to broaden the search strategy. Predefined keywords, including "Irritable bowel syndrome" (MeSH) OR "IBS" (all fields), along with "Saudi Arabia" and "Middle East," were used to avoid data loss and ambiguity. Any cross-sectional study that reported the prevalence of IBS in any gender, age, and group of the Saudi population was included. Data extraction was independently performed in duplicate to mitigate bias and data loss. Statistical analysis of proportion was conducted by using Miller (Freeman-Tukey double arcsine - exact inverse). Out of 350 records identified, only 38 studies were included in the quantitative synthesis. The total number of study participants was 26,567, on the basis of the predefined inclusion criteria of the study. StatsDirect software was used for the statistical analysis of the study parameters. Based on all 38 identified studies, the calculated pooled prevalence was 20.7% (95% confidence interval (CI) = 17.8% to 23.7% by applying random effects (DerSimonian-Laird method). IBS was identified in 21% (95% CI = 16.7% to 25.7%) of the general population, 22% (95% CI = 17.6% to 26.7%) of students, and 18.3% (95% CI = 13.3% to 23.9%) of healthcare workers. The pooled prevalence of IBS among the Saudi population was 20.7%. The pathophysiology of IBS is complexed and significantly affected by genetics, diet, cultural characteristics, age, anxiety, depression, stress, and sleep disorders. This study fills a gap in understanding IBS prevalence in Saudi Arabia, contributing valuable data to this region.

Dhafar, M. K., F. Y. Bahakeem, A. H. Alsehli, R. S. Kofyah, R. E. Hamad, W. I. Faraj, B. S. Alsalem, and M. A. Elhefny, "Parental Awareness of Headaches Among Elementary School-Aged Children in Makkah, Saudi Arabia: A Cross-Sectional Study.", Cureus, vol. 15, issue 8, pp. e44331, 2023. Abstractparental_awareness_of_headaches_among_elementary_school-aged_children_in_makkah_saudi_arabia-_a_cross-sectional_study.pdf

Background Headaches are a prevalent form of pain experienced in the skull, face, and facial structures, categorized into two types: primary and secondary. Primary headaches are more frequently observed in children and can be triggered by sleep disturbances, vision problems, malnutrition, and other medical conditions. Despite their prevalence among children, these headaches often go unrecognized and untreated, and there seems to be insufficient parental awareness regarding childhood headaches. This study aims to determine the prevalence of childhood headaches and assess awareness about this among parents of elementary school-aged children in Makkah, Saudi Arabia, to enhance parental understanding of this issue. Methods Data were collected through an online survey created using Google Forms (Google LLC, Mountain View, California, United States), distributed to parents residing in Makkah. The survey was disseminated in March 2023. Results A total of 499 parents completed the study questionnaire, comprising 399 mothers and 100 fathers, with a mean parental age of 37.1 ± 13.9 years. Of the participants, 89.2% were married, 91% were Saudi nationals, and 105 had secondary education. Parents reported that 13.2% of their children complained of headaches, with 55.3% describing them as occasional. Among the respondents, 178 parents sought medical care for their children's headaches primarily out of fear. It was found that 69.7% of parents with higher education had good knowledge regarding childhood headaches, while 59.8% of employed parents had good knowledge compared to 43.8% of others. Conclusion This study revealed a lack of adequate knowledge and awareness among parents regarding headaches in children residing in Makkah. Therefore, we recommend conducting further research and implementing educational initiatives to enhance parental understanding of childhood headaches in Makkah and other regions of Saudi Arabia.

Salama, B., K. J. Alzahrani, K. S. Alghamdi, O. Al-Amer, K. E. Hassan, M. A. Elhefny, A. J. A. Albarakati, F. Alharthi, H. A. Althagafi, H. Al Sberi, et al., "Silver Nanoparticles Enhance Oxidative Stress, Inflammation, and Apoptosis in Liver and Kidney Tissues: Potential Protective Role of Thymoquinone.", Biological trace element research, vol. 201, issue 6, pp. 2942-2954, 2023. Abstractsilver_nanoparticles_enhance_oxidative_stress_inflammation_and_apoptosis_in_liver_and_kidney_tissues-_potential_protective_role_of_thymoquinone.pdf

Silver nanoparticles (AgNPs) are the most common nanomaterials in consumer products. Therefore, it has been crucial to control AgNPs toxicological effects to improve their safety and increase the outcome of their applications. This work investigated the possible protective effect of thymoquinone (TQ) against AgNPs-induced hepatic and renal cytotoxicity in rats. Serum markers of liver and kidney functions as well as liver and kidney oxidative stress status, pro-inflammatory cytokines, apoptosis markers, and histopathology were assessed. TQ reversed AgNPs-induced elevation in serum liver and kidney function markers, including aspartate transaminase, alanine transaminase, urea, and creatinine. Moreover, TQ co-administration with AgNPs alleviates hepatic and renal oxidative insults by decreasing MDA and NO levels with a significant increase in the activity of antioxidant enzymes (superoxide dismutase, catalase, and glutathione recycling enzymes peroxidase and reductase) compared to AgNPs-treated rats. Besides, TQ upregulated hepatic and renal Nrf2 gene expression in AgNPs-intoxicated rats. Furthermore, TQ co-administration decreased the hepatic and renal pro-inflammatory mediators represented by IL-1β, TNF-α, TGF-β, and NF-κB levels. Besides, TQ co-administration decreased apoptotic protein (Bax) levels and increased the anti-apoptotic protein (Bcl-2) levels. These findings were confirmed by the histopathological examination of hepatic and renal tissues. Our data affirmed the protective effect of TQ against AgNPs cytotoxicity and proposed a possible mechanism of TQ antioxidant, anti-inflammatory, and anti-apoptotic effects. Consequently, we could conclude that using TQ might control AgNPs toxicological effects, improve their safety, and increase the outcome of their applications.

Li, L., H. Ma, Y. Zhang, H. Jiang, B. Xia, H. Al Sberi, M. A. Elhefny, M. S. Lokman, and R. B. Kassab, "Protocatechuic acid reverses myocardial infarction mediated by β-adrenergic agonist via regulation of Nrf2/HO-1 pathway, inflammatory, apoptotic, and fibrotic events.", Journal of biochemical and molecular toxicology, vol. 37, issue 3, pp. e23270, 2023. Abstractprotocatechuic_acid_reverses_myocardial_infarction_mediated_by_b-adrenergic_agonist_via_regulation_of_nrf2-ho-1_pathway_inflammatory_apoptotic_and_fibrotic_events.pdf

Myocardial infarction (MI) is an instant ischemic death of cardiomyocytes that remains a major global cause of mortalities. MI is accompanied by oxidative, inflammatory, apoptotic, and fibrotic insults. Protocatechuic acid (PCA) is a polyphenolic compound with various potent biological activities. In this study, we explored the possible cardioprotective role of PCA against isoproterenol (ISO)-mediated MI. Rats were either injected with ISO (85 mg/kg, subcutaneously) or pretreated with PCA (100 or 200 mg/kg, orally). PCA supplementation markedly normalized ISO-induced disturbed cardiac function markers (creatine kinase-MB, lactate dehydrogenase, and troponin T). Notably, PCA administration exerted remarkable increases in glutathione and its derived enzymes, superoxide dismutase, and catalase, as well as decreases in malondialdehyde and nitric oxide levels in the injured cardiac tissue. The molecular findings validated the augmented cellular antioxidative capacity by PCA via increasing the gene expressions of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1. The cardioprotective efficacy of PCA extended to suppress cardiac inflammation as demonstrated by the decreased levels of tumor necrosis factor-alpha, interleukin-1 beta, and nuclear factor kappa B. Additionally, PCA prevented cardiomyocyte loss and fibrosis by decreasing Bax, caspase-3, transforming growth factor-β1 and matrix metalloproteinase-9, and enhancing B-cell lymphoma 2 and tissue inhibitors of metalloproteinase-3. The cardiac histological screening further confirmed the PCA's protective action. The obtained data recommend PCA as an alternative therapeutic agent to attenuate the molecular, biochemical, and histological alterations associated with MI development.

Lokman, M. S., H. A. Althagafi, F. Alharthi, O. A. Habotta, A. A. Hassan, M. A. Elhefny, H. Al Sberi, A. Theyab, A. H. Mufti, A. Alhazmi, et al., "Protective effect of quercetin against 5-fluorouracil-induced cardiac impairments through activating Nrf2 and inhibiting NF-κB and caspase-3 activities.", Environmental science and pollution research international, vol. 30, issue 7, pp. 17657-17669, 2023. Abstractprotective_effect_of_quercetin_against_5-fluorouracil-induced_cardiac_impairments_through_activating_nrf2_and_inhibiting_nf-kb_and_caspase-3_activities.pdf

5-Fluorouracil (5-FU) is a chemotherapy used to treat many types of cancer. Cardiotoxicity is one of the common drawbacks of 5-FU therapy. Quercetin (Qu) is a bioflavonoid with striking biological activities. This research aimed to assess the ameliorative effect of Qu against 5-FU-mediated cardiotoxicity. Thirty-five rats were allocated into five groups: control group (normal saline), 5-FU group (30 mg/kg, intraperitoneally), Qu group (50 mg/kg, oral), 25 mg/kg Qu+5-FU group, and 50 mg/kg Qu+5-FU. The experimental animals were received the above-mentioned drugs for 21 days. Results showed that 5-FU significantly elevated creatine kinase, lactate dehydrogenase, serum cholesterol and triglyceride, and upregulated troponin and renin mRNA expression. Additionally, cardiac oxidant/antioxidant imbalance was evident in elevated oxidants (malondialdehyde and nitric oxide) and depleted antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). 5-FU also downregulated the gene expression of nuclear factor erythroid 2-related factor 2. Furthermore, 5-FU significantly increased cardiac pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and upregulated gene expression of nuclear factor kappa-B. 5-FU significantly enhanced cardiac apoptosis through upregulating caspase-3 expression and downregulating B-cell lymphoma 2. Immunohistochemical and histopathological examinations verified the above-mentioned findings. However, all these changes were significantly ameliorated in Qu pre-administered rats. Conclusively, Qu counteracted 5-FU-mediated cardiotoxicity through potent antioxidant, anti-inflammatory, and anti-apoptotic effects.