Kareem Mohamed Mostafa Saad
@mans.edu.eg
Pharmacology and Toxicology Department, Faculty of Pharmacy
Mansoura University
EDUCATION
Masters degree in pharmaceutical sciences (Pharmacology and Toxicology)
RESEARCH INTERESTS
I am interested in inflammation process as a reason for many diseases with its subsequent events including oxidative stress, chemotaxis, and cellular signalling.
Scopus Publications
Scholar Citations
Scholar h-index
Scholar i10-index
Scopus Publications
Mahmoud Elashiry, Celine Joyce Cornelius Timothius, Rizwana Zaman, Marisa Elliott, Bryce Crosby, Keshav Bhat, Karim M. Saad, and Ranya Elsayed
MDPI AG
Cellular senescence is a fundamental biological process characterized by stable cell cycle arrest, resistance to apoptosis, and the acquisition of a pro-inflammatory senescence-associated secretory phenotype (SASP). While senescence plays essential roles in development, tissue homeostasis, and tumor suppression, its accumulation with age and chronic stress contributes to tissue dysfunction and disease. In the oral cavity, where tissues are continuously exposed to mechanical stress, microbial challenge, and environmental insults, senescence has emerged as a critical regulator of both health and pathology. This review provides an overview of the defining hallmarks of cellular senescence, the molecular mechanisms driving its onset, and its physiological and pathological consequences, with a particular focus on oral tissues. We highlight the beneficial roles of senescence in maintaining oral tissue integrity, facilitating wound repair, suppressing malignant transformation, and promoting immune-mediated clearance of damaged cells. Conversely, we discuss the detrimental effects of persistent senescent cell accumulation, including oral aging phenotypes, chronic inflammation, alveolar bone loss, periodontal breakdown, salivary gland dysfunction, and contributions to oral carcinogenesis. Finally, we examine emerging therapeutic strategies targeting senescence in oral disease management, including senolytic and senomorphic approaches, immune-based clearance mechanisms, and gene- and cell-based interventions aimed at delaying or modulating senescence. Understanding the dualistic nature of cellular senescence in the oral environment may inform novel preventive and therapeutic strategies to promote oral health and mitigate age- and disease-associated oral pathologies.
Karim M. Saad, Mohamed S. Gad, Jocelyn Tang, Kim Capehart, Rafik Abdelsayed, Jan M. Williams, and Ahmed A. Elmarakby
MDPI AG
Background: Obesity is a major contributor to chronic kidney disease (CKD) through mechanisms involving inflammation and metabolic dysregulation. Premenopausal female rats are known to be protected from cardiovascular disorders vs. age matched male rats. The current study investigates if there are sex differences in obesity-induced renal inflammation in SS leptin receptor mutant (SSLepR mutant) rats as a model of metabolic syndrome. Method: Male and female lean and obese SSLepR mutant rats were used in the current study to assess changes in metabolic parameters and markers of renal inflammation. Results: Obese SSLepR rats showed significant increases in body weight, hemoglobin A1c (HbA1c), and cholesterol vs. lean control, although their blood glucose levels remained comparable to lean rats. Plasma leptin, insulin, and TNF-α converting enzyme (TACE) levels were significantly elevated in obese SSLepR rats vs. lean control rats, with no apparent sex differences. Obesity was associated with an elevation in renal injury since protein and albumin excretion levels were significantly elevated in obese SSLepR rats vs. lean control rats, with no apparent sex differences. The elevation in renal injury was associated with increased renal fibrosis as evidenced by increased collagen deposition and TGF-β expression in the kidney of obese SSLepR rats vs. lean control rats. Increased renal fibrosis also coincided with increased renal inflammation and apoptosis as evidenced by increased macrophage infiltration and IL-6 expression in the kidneys of obese SSLepR rats vs. lean control rats. Conclusion: These findings indicate that obesity triggers renal inflammation and fibrosis independent of hyperglycemia in SSLepR rats, and these changes may override sex-based protective effects seen in females in other experimental rodent models of cardiovascular diseases.
Karim M. Saad, Khaled Elmasry, Babak Baban, Man J. Livingston, Zheng Dong, Marwa E. Abdelmageed, Rania R. Abdelaziz, Ghada M. Suddek, and Ahmed A. Elmarakby
MDPI AG
Cisplatin is a highly cytotoxic drug used for the treatment of head, neck, and soft tissue cancers; however, it has nephrotoxic effects that can lead to acute kidney injury. Protocatechuic acid (PCA) is a natural widely available antioxidant found in many fruits such as kiwi, mango, and berries. We have recently shown that PCA reduced renal injury in a mouse model of unilateral ureteral obstruction. The current study aims to investigate the protective effects of PCA in Cisplatin-induced inflammation in vitro in Boston University Mouse Proximal Tubular (BUMPT) cells. BUMPT cells were cultured in complete DMEM. Confluent BUMPT cells were then treated with 20 μM Cisplatin ± PCA 50 or 100 μM for 24 h. PCA treatment showed a dose-depending increase in % cell viability in Cisplatin-treated BUMPT cells. PCA treatment also dose-dependently decreased Cisplatin-induced increases in oxidative stress (ROS and TBARS), inflammation (p-NF-κB and IL-6), and apoptosis (cleaved caspase-3 and % of TUNEL+ cells) compared to Cisplatin-only treatment. The reduction in oxidative stress, inflammation, and apoptosis with PCA treatment in Cisplatin-treated BUMPT cells was associated with decreases in tubular physical barrier resistance and the expression of the tight junction protein zonula occludens-1 (ZO-1) when compared to BUMPT cells treated with Cisplatin alone. The current findings suggest that PCA treatment improves tubular barrier function in Cisplatin-treated BUMPT cells via reductions in oxidative stress, inflammation, and apoptosis.
Sara H. Hazem, Karim M. Saad, and Mahmoud M. Samaha
Elsevier BV
Abdulmohsin Alhashim, Kim Capehart, Jocelyn Tang, Karim M. Saad, Rafik Abdelsayed, Marion A. Cooley, Jan M. Williams, and Ahmed A. Elmarakby
MDPI AG
Introduction: The incidence of obesity has dramatically increased worldwide. Obesity has been shown to exacerbate the progression of periodontal disease. Studies suggest a sex difference in periodontitis, whereby males are more sensitive to periodontal inflammation compared to females. Aim: In the current study, it was hypothesized that obesity drives periodontal inflammation and bone loss in both sexes. Methodology: Utilizing leptin receptor mutant (SSLepR mutant) rats as a genetic model of obesity, 11–12-week-old male and female lean Dahl salt-sensitive (SS) rats and obese SSLepR mutant rats were used to investigate sex differences in obesity-induced periodontal inflammation. Results: Body weight, insulin, hemoglobin A1c and cholesterol levels were significantly elevated in the obese SSLepR mutant strain vs. the lean SS strain within the same sex. Sex differences in body weight and plasma hemoglobin A1c were only observed in obese SSLepR mutant rats, with males having significantly greater body weight and hemoglobin A1c vs. females. Plasma thiobarbituric acid reactive substances (TBARs) and monocyte chemoattractant protein-1 (MCP-1), markers of systemic oxidative stress and inflammation, respectively, were significantly elevated in obese SSLepR mutant rats vs. lean SS rats, with no sex differences in these parameters in either rat strains. Although micro-CT analyses of the maxillary first molar alveolar bone from obese SSLepR mutant rats revealed no evidence of bone loss and/or sex differences, immuno-histochemical analysis revealed significant elevations in periodontal IL-6 and decreases in IL-10 in obese SSLepR mutant rats vs. lean SS rats, with no apparent sex differences in these parameters. Conclusions: Obesity increases systemic and periodontal inflammation, without evidence of bone loss or apparent sex differences in SSLepR mutant rats.
Karim M. Saad, Évila Lopes Salles, Sahar Emami Naeini, Babak Baban, Marwa E. Abdelmageed, Rania R. Abdelaziz, Ghada M. Suddek, and Ahmed A. Elmarakby
Springer Science and Business Media LLC
Abigayle B. Simon, Cassandra C. Derella, Marsha Blackburn, Jeffrey Thomas, Lawrence C. Layman, Matthew S. Nicholson, Jennifer Waller, Ahmed Elmarakby, Karim M. Saad, and Ryan A. Harris
Springer Science and Business Media LLC
Abstract Background Endogenous estrogen is cardio-protective in healthy premenopausal women. Despite this favorable action of estrogen, animal models depict a detrimental effect of estradiol on vascular function in the presence of diabetes. The present study sought to determine the role of endogenous estradiol on endothelial function in women with type 1 diabetes. Method 32 women with type 1 diabetes (HbA1c = 8.6 ± 1.7%) and 25 apparently healthy women (HbA1c = 5.2 ± 0.3%) participated. Flow-mediated dilation (FMD), a bioassay of nitric-oxide bioavailability and endothelial function was performed during menses (M) and the late follicular (LF) phase of the menstrual cycle to represent low and high concentrations of estrogen, respectively. In addition, a venous blood sample was collected at each visit to determine circulating concentrations of estradiol, thiobarbituric acid reactive substances (TBARS), and nitrate/nitrite (NOx), biomarkers of oxidative stress and nitric oxide, respectively. Data were collected in (1) 9 additional women with type 1 diabetes using oral hormonal birth control (HBC) (HbA1c = 8.3 ± 2.1%) during the placebo pill week and second active pill week, and (2) a subgroup of 9 demographically matched women with type 1 diabetes not using HBC (HbA1c = 8.9 ± 2.1%). Results Overall, estradiol was significantly increased during the LF phase compared to M in both type 1 diabetes (Δestradiol = 75 ± 86 pg/mL) and controls (Δestradiol = 71 ± 76 pg/mL); however, an increase in TBARS was only observed in patients with type 1 diabetes (ΔTBARS = 3 ± 13 µM) compared to controls (ΔTBARS = 0 ± 4 µM). FMD was similar (p = 0.406) between groups at M. In addition, FMD increased significantly from M to the LF phase in controls (p = 0.024), whereas a decrease was observed in type 1 diabetes. FMD was greater (p = 0.015) in patients using HBC compared to those not on HBC, independent of menstrual cycle phase. Conclusion Endogenous estradiol increases oxidative stress and contributes to endothelial dysfunction in women with diabetes. Additionally, HBC use appears to be beneficial to endothelial function in type 1 diabetes.
Ahmed A. Elmarakby, Karim M. Saad, G. Ryan Crislip, and Jennifer C. Sullivan
Wiley
AbstractNitric oxide (NO) contributes to blood pressure (BP) regulation via its vasodilatory and anti‐inflammatory properties. We and others previously reported sex differences in BP in normotensive and hypertensive rat models where females have lower BP than age‐matched males. As females are known to have greater NO bioavailability than age‐matched males, the current study was designed to test the hypothesis that anesthetized female normotensive Wistar Kyoto rats (WKY) are more responsive to acute NOS inhibition‐induced increases in BP compared to male WKY. Twelve‐week‐old male and female WKY were randomized to infusion of the nonspecific NOS inhibitor NG‐nitro‐L‐arginine methyl ester (L‐NAME, 1 mg/kg/min) or selective NOS1 inhibition with vinyl‐L‐NIO (VNIO, 0.5 mg/kg/min) for 60 min. Mean arterial BP, glomerular filtration rate (GFR), urine volume, and electrolyte excretion were assessed before, and during L‐NAME or VNIO infusion. L‐NAME and VNIO significantly increased BP in both sexes; however, the increase in BP with L‐NAME infusion was greater in females versus males compared to baseline BP values. Acute infusion of neither L‐NAME nor VNIO for 60 min altered GFR in either sex. However, urine volume, sodium, chloride and potassium excretion levels increased comparably in male and female WKY with L‐NAME and VNIO infusion. Our findings suggest sex differences in BP responses to acute non‐isoform‐specific NOS inhibition in WKY, with females being more responsive to L‐NAME‐induced elevations in BP relative to male WKY. However, sex differences in the BP response did not coincide with sex differences in renal hemodynamic responses to acute NOS inhibition.
Omnia M. Waly, Kareem M. Saad, Hussein I. El-Subbagh, Said M. Bayomi, and Mariam A. Ghaly
Elsevier BV
Kareem M. Saad, Rehab S. Abdelrahman, and Eman Said
Elsevier BV
Cisplatin is an effective anticancer used widely in treatment of solid and germ cell tumors, however, the immense toxicity on healthy tissues discourages cisplatin use in prolonged treatment protocols. Testicular toxicity is amongst its undesired adverse effects. Nilotinib is a second generation multityrosine kinase inhibitor which is used as an anticancer agent with anti-inflammatory and antioxidant activities. In the present study, a single dose of cisplatin (7 mg/kg, I.P) to rats induced a significant testicular injury. Daily administration of nilotinib (20 mg/kg, orally) 24 h post cisplatin injection for 10 days ameliorated testicular damage. Nilotinib significantly increased serum testosterone and sperm concentration outside frame of oligospermia with simultaneous full recovery of sperm viability. Nevertheless, biomarkers of apoptosis such as JNKs and Caspase -3, were significantly reduced. Moreover, improved antioxidant status of the testes was inferred by significant elevation of GSR, SOD and TAC alongside with reduction in lipid peroxidation biomarkers; MDA and 4-HNE. Flow Cytometry analysis of the cell cycle confirmed a significant increase in the percentage of testicular cells present in G2/M phase and a significant decrease in the percentage of apoptotic testicular cells after nilotinib administration. Histopathologically, nilotinib preserved testicular architecture showing significant numbers of sperm and spermatids within lumens of seminiferous tubule. Furthermore, nilotinib enhanced testicular expression of Ki67 significantly, providing evidence of testicular regeneration. In conclusion, nilotinib refinement of cisplatin induced testicular toxicity is attributed to enhancing antioxidant capabilities, decreasing apoptotic signals and restoring regenerative capacity of testes suggesting nilotinib to be used in conjunction with cisplatin in treatment protocols to avoid cisplatin induced long term testicular toxicity.
Kareem M. Saad, Mohamed E. Shaker, Ahmed A. Shaaban, Rehab S. Abdelrahman, and Eman Said
Elsevier BV
Acetaminophen (APAP)-induced hepatotoxicity comes among the most frequent humans' toxicities caused by drugs. So far, therapeutic interventions for such type of drug-induced toxicity are still limited. In the current study, we examined the influence of capmatinib (Cap), a novel c-Met inhibitor, on APAP-induced hepatotoxicity in mice when administered 2 h prior, 2 h post and 4 h post APAP-challenge. The results revealed that Cap administration significantly attenuated APAP-induced liver injury when administered only 2 h prior and post APAP-administration. Cap hepatoprotective effect was mediated by lowering the excessive formation of lipid peroxidation and nitrosative stress products caused by APAP. Besides, Cap attenuated APAP-induced overproduction and release of proinflammatory mediators like TNF-α, IL-1β, IL-17A, IL-6, and MCP-1. Cap treatment also led to avoidance of APAP-subsequent repair by abating APAP-induced elevation of hepatic IL-22 and PCNA expressions. In conclusion, c-Met receptor inhibition may be a potential strategy for alleviating APAP-hepatotoxicity, especially when administered in the early phase of intoxication.
RECENT SCHOLAR PUBLICATIONS
B Crosby, A Carroll, J Williams, K Saad, R Zaman, R El Sayed
Augusta University , 2026
2026
M Elashiry, CJ Cornelius Timothius, R Zaman, M Elliott, B Crosby, K Bhat, ...
International journal of molecular sciences 27 (5), 2269 , 2026
2026
Citations: 3
KM Saad, MS Gad, J Tang, K Capehart, R Abdelsayed, JM Williams, ...
Biomedicines 13 (1), 3105 , 2025
2025
KM Saad, K Elmasry, B Baban, MJ Livingston, Z Dong, ME Abdelmageed, ...
International journal of molecular sciences 26 (9), 4115 , 2025
2025
Citations: 3
SH Hazem, KM Saad, MM Samaha
International Immunopharmacology 149, 114256 , 2025
2025
Citations: 6
A Alhashim, K Capehart, J Tang, KM Saad, R Abdelsayed, MA Cooley, ...
Dentistry Journal 13 (1), 14 , 2024
2024
Citations: 4
KM Saad, ÉL Salles, SE Naeini, B Baban, ME Abdelmageed, ...
Pharmacological Reports 76 (1), 98-111 , 2024
2024
Citations: 10
SE Naeini, E Salles, B Bhandari, KM Saad, S Rezaee, AA Elmarakby, ...
Journal of the American Society of Nephrology 34 (11S), 646 , 2023
2023
AB Simon, CC Derella, M Blackburn, J Thomas, LC Layman, ...
Cardiovascular Diabetology 22 (1), 243 , 2023
2023
Citations: 12
KM Saad, E Da Silva Lopes Salle, S Emami Naeini, B Baban, ...
Hypertension 80 (Suppl_1), AP127-AP127 , 2023
2023
AA Elmarakby, KM Saad, GR Crislip, JC Sullivan
Physiological reports 11 (15), e15771 , 2023
2023
Citations: 3
OM Waly, KM Saad, HI El-Subbagh, SM Bayomi, MA Ghaly
European Journal of Medicinal Chemistry 231, 114152 , 2022
2022
Citations: 36
KM Saad, RS Abdelrahman, E Said
Environmental Toxicology and Pharmacology 76, 103334 , 2020
2020
Citations: 25
KM Saad, ME Shaker, RS Abdelrahman, AA Shaaban, E Said
International Immunopharmacology 81 (April2020), 106292 , 2020
2020
Citations: 24
MOST CITED SCHOLAR PUBLICATIONS
OM Waly, KM Saad, HI El-Subbagh, SM Bayomi, MA Ghaly
European Journal of Medicinal Chemistry 231, 114152 , 2022
2022
Citations: 36
KM Saad, RS Abdelrahman, E Said
Environmental Toxicology and Pharmacology 76, 103334 , 2020
2020
Citations: 25
KM Saad, ME Shaker, RS Abdelrahman, AA Shaaban, E Said
International Immunopharmacology 81 (April2020), 106292 , 2020
2020
Citations: 24
AB Simon, CC Derella, M Blackburn, J Thomas, LC Layman, ...
Cardiovascular Diabetology 22 (1), 243 , 2023
2023
Citations: 12
KM Saad, ÉL Salles, SE Naeini, B Baban, ME Abdelmageed, ...
Pharmacological Reports 76 (1), 98-111 , 2024
2024
Citations: 10
SH Hazem, KM Saad, MM Samaha
International Immunopharmacology 149, 114256 , 2025
2025
Citations: 6
A Alhashim, K Capehart, J Tang, KM Saad, R Abdelsayed, MA Cooley, ...
Dentistry Journal 13 (1), 14 , 2024
2024
Citations: 4
M Elashiry, CJ Cornelius Timothius, R Zaman, M Elliott, B Crosby, K Bhat, ...
International journal of molecular sciences 27 (5), 2269 , 2026
2026
Citations: 3
KM Saad, K Elmasry, B Baban, MJ Livingston, Z Dong, ME Abdelmageed, ...
International journal of molecular sciences 26 (9), 4115 , 2025
2025
Citations: 3
AA Elmarakby, KM Saad, GR Crislip, JC Sullivan
Physiological reports 11 (15), e15771 , 2023
2023
Citations: 3
B Crosby, A Carroll, J Williams, K Saad, R Zaman, R El Sayed
Augusta University , 2026
2026
KM Saad, MS Gad, J Tang, K Capehart, R Abdelsayed, JM Williams, ...
Biomedicines 13 (1), 3105 , 2025
2025
SE Naeini, E Salles, B Bhandari, KM Saad, S Rezaee, AA Elmarakby, ...
Journal of the American Society of Nephrology 34 (11S), 646 , 2023
2023
KM Saad, E Da Silva Lopes Salle, S Emami Naeini, B Baban, ...
Hypertension 80 (Suppl_1), AP127-AP127 , 2023
2023
Publications
Mechanistic perspective of protective effects of nilotinib against cisplatin-induced testicular injury in rats: Role of JNK/caspase-3 signaling inhibition
The c-Met inhibitor capmatinib alleviates acetaminophen-induced hepatotoxicity