Kareem Mohamed Mostafa Saad

@mans.edu.eg

Pharmacology and Toxicology Department, Faculty of Pharmacy
Mansoura University

Kareem Mohamed Mostafa Saad


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https://researchid.co/kareemsaad

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.
11

Scopus Publications

126

Scholar Citations

6

Scholar h-index

5

Scholar i10-index

Scopus Publications

  • The Role of Cellular Senescence in Oral Health and Disease
    Mahmoud Elashiry, Celine Joyce Cornelius Timothius, Rizwana Zaman, Marisa Elliott, Bryce Crosby, et al.
    International Journal of Molecular Sciences, 2026
    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.
  • Obesity Promotes Renal Inflammation and Fibrosis Independent of Sex in SS Leptin Receptor Mutant (SSLepR) Rats
    Karim M. Saad, Mohamed S. Gad, Jocelyn Tang, Kim Capehart, Rafik Abdelsayed, et al.
    Biomedicines, 2025
    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.
  • Protocatechuic Acid Ameliorates Cisplatin-Induced Inflammation and Apoptosis in Mouse Proximal Tubular Cells
    Karim M. Saad, Khaled Elmasry, Babak Baban, Man J. Livingston, Zheng Dong, et al.
    International Journal of Molecular Sciences, 2025
    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.
  • Protective effects of BTK inhibition by acalabrutinib on cisplatin-induced renal and testicular injury in mice: Modulation of mTOR/AMPK, NLRP3/GSDMD-N, and apoptotic pathways.
    Sara H. Hazem, Karim M. Saad, Mahmoud M. Samaha
    International Immunopharmacology, 2025
  • Does Sex Matter in Obesity-Induced Periodontal Inflammation in the SSLepR Mutant Rats?
    Abdulmohsin Alhashim, Kim Capehart, Jocelyn Tang, Karim M. Saad, Rafik Abdelsayed, et al.
    Dentistry Journal, 2025
    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.
  • Reno-protective effect of protocatechuic acid is independent of sex-related differences in murine model of UUO-induced kidney injury
    Karim M. Saad, Évila Lopes Salles, Sahar Emami Naeini, Babak Baban, Marwa E. Abdelmageed, et al.
    Pharmacological Reports, 2024
  • Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes
    Abigayle B. Simon, Cassandra C. Derella, Marsha Blackburn, Jeffrey Thomas, Lawrence C. Layman, et al.
    Cardiovascular Diabetology, 2023
    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.
  • Acute nitric oxide synthase inhibition induces greater increases in blood pressure in female versus male Wistar Kyoto rats
    Ahmed A. Elmarakby, Karim M. Saad, G. Ryan Crislip, Jennifer C. Sullivan
    Physiological Reports, 2023
    Nitric 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.
  • Synthesis, biological evaluation, and molecular modeling simulations of new heterocyclic hybrids as multi-targeted anti-Alzheimer's agents
    Omnia M. Waly, Kareem M. Saad, Hussein I. El-Subbagh, Said M. Bayomi, Mariam A. Ghaly
    European Journal of Medicinal Chemistry, 2022
  • Mechanistic perspective of protective effects of nilotinib against cisplatin-induced testicular injury in rats: Role of JNK/caspase-3 signaling inhibition
    Kareem M. Saad, Rehab S. Abdelrahman, Eman Said
    Environmental Toxicology and Pharmacology, 2020
    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.
  • The c-Met inhibitor capmatinib alleviates acetaminophen-induced hepatotoxicity
    Kareem M. Saad, Mohamed E. Shaker, Ahmed A. Shaaban, Rehab S. Abdelrahman, Eman Said
    International Immunopharmacology, 2020

RECENT SCHOLAR PUBLICATIONS

  • Periodontitis Promotes Brain Aging: Insights from the p16-3MR Senescence Reporter Mouse
    B Crosby, A Carroll, J Williams, K Saad, R Zaman, R El Sayed
    Augusta University , 2026
    2026
  • The role of cellular senescence in oral health and disease
    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
  • Obesity Promotes Renal Inflammation and Fibrosis Independent of Sex in SS Leptin Receptor Mutant (SSLepR) Rats
    KM Saad, MS Gad, J Tang, K Capehart, R Abdelsayed, JM Williams, ...
    Biomedicines 13 (1), 3105 , 2025
    2025
  • Protocatechuic acid ameliorates cisplatin-induced inflammation and apoptosis in mouse proximal tubular cells
    KM Saad, K Elmasry, B Baban, MJ Livingston, Z Dong, ME Abdelmageed, ...
    International journal of molecular sciences 26 (9), 4115 , 2025
    2025
    Citations: 3
  • Protective effects of BTK inhibition by acalabrutinib on cisplatin-induced renal and testicular injury in mice: Modulation of mTOR/AMPK, NLRP3/GSDMD-N, and apoptotic pathways.
    SH Hazem, KM Saad, MM Samaha
    International Immunopharmacology 149, 114256 , 2025
    2025
    Citations: 6
  • Does Sex Matter in Obesity-Induced Periodontal Inflammation in the SS LepR Mutant Rats?
    A Alhashim, K Capehart, J Tang, KM Saad, R Abdelsayed, MA Cooley, ...
    Dentistry Journal 13 (1), 14 , 2024
    2024
    Citations: 4
  • Reno-protective effect of protocatechuic acid is independent of sex-related differences in murine model of UUO-induced kidney injury
    KM Saad, ÉL Salles, SE Naeini, B Baban, ME Abdelmageed, ...
    Pharmacological Reports 76 (1), 98-111 , 2024
    2024
    Citations: 10
  • Maternal Exposure to Tetrahydrocannabinol (THC) During Pregnancy Increases Kidney Damage in Mouse Offspring
    SE Naeini, E Salles, B Bhandari, KM Saad, S Rezaee, AA Elmarakby, ...
    Journal of the American Society of Nephrology 34 (11S), 646 , 2023
    2023
  • Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes
    AB Simon, CC Derella, M Blackburn, J Thomas, LC Layman, ...
    Cardiovascular Diabetology 22 (1), 243 , 2023
    2023
    Citations: 12
  • Abstract P127: Protective Effects Of Protocatechuic Acid In Murine Model Of UUO-induced Renal Injury
    KM Saad, E Da Silva Lopes Salle, S Emami Naeini, B Baban, ...
    Hypertension 80 (Suppl_1), AP127-AP127 , 2023
    2023
  • Acute nitric oxide synthase inhibition induces greater increases in blood pressure in female versus male Wistar Kyoto rats
    AA Elmarakby, KM Saad, GR Crislip, JC Sullivan
    Physiological reports 11 (15), e15771 , 2023
    2023
    Citations: 3
  • Synthesis, biological evaluation, and molecular modeling simulations of new heterocyclic hybrids as multi-targeted anti-Alzheimer's agents
    OM Waly, KM Saad, HI El-Subbagh, SM Bayomi, MA Ghaly
    European Journal of Medicinal Chemistry 231, 114152 , 2022
    2022
    Citations: 36
  • Mechanistic perspective of protective effects of nilotinib against cisplatin-induced testicular injury in rats: Role of JNK/caspase-3 signaling inhibition
    KM Saad, RS Abdelrahman, E Said
    Environmental Toxicology and Pharmacology 76, 103334 , 2020
    2020
    Citations: 25
  • The c-Met inhibitor capmatinib alleviates acetaminophen-induced hepatotoxicity
    KM Saad, ME Shaker, RS Abdelrahman, AA Shaaban, E Said
    International Immunopharmacology 81 (April2020), 106292 , 2020
    2020
    Citations: 24

MOST CITED SCHOLAR PUBLICATIONS

  • Synthesis, biological evaluation, and molecular modeling simulations of new heterocyclic hybrids as multi-targeted anti-Alzheimer's agents
    OM Waly, KM Saad, HI El-Subbagh, SM Bayomi, MA Ghaly
    European Journal of Medicinal Chemistry 231, 114152 , 2022
    2022
    Citations: 36
  • Mechanistic perspective of protective effects of nilotinib against cisplatin-induced testicular injury in rats: Role of JNK/caspase-3 signaling inhibition
    KM Saad, RS Abdelrahman, E Said
    Environmental Toxicology and Pharmacology 76, 103334 , 2020
    2020
    Citations: 25
  • The c-Met inhibitor capmatinib alleviates acetaminophen-induced hepatotoxicity
    KM Saad, ME Shaker, RS Abdelrahman, AA Shaaban, E Said
    International Immunopharmacology 81 (April2020), 106292 , 2020
    2020
    Citations: 24
  • Endogenous estradiol contributes to vascular endothelial dysfunction in premenopausal women with type 1 diabetes
    AB Simon, CC Derella, M Blackburn, J Thomas, LC Layman, ...
    Cardiovascular Diabetology 22 (1), 243 , 2023
    2023
    Citations: 12
  • Reno-protective effect of protocatechuic acid is independent of sex-related differences in murine model of UUO-induced kidney injury
    KM Saad, ÉL Salles, SE Naeini, B Baban, ME Abdelmageed, ...
    Pharmacological Reports 76 (1), 98-111 , 2024
    2024
    Citations: 10
  • Protective effects of BTK inhibition by acalabrutinib on cisplatin-induced renal and testicular injury in mice: Modulation of mTOR/AMPK, NLRP3/GSDMD-N, and apoptotic pathways.
    SH Hazem, KM Saad, MM Samaha
    International Immunopharmacology 149, 114256 , 2025
    2025
    Citations: 6
  • Does Sex Matter in Obesity-Induced Periodontal Inflammation in the SS LepR Mutant Rats?
    A Alhashim, K Capehart, J Tang, KM Saad, R Abdelsayed, MA Cooley, ...
    Dentistry Journal 13 (1), 14 , 2024
    2024
    Citations: 4
  • The role of cellular senescence in oral health and disease
    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
  • Protocatechuic acid ameliorates cisplatin-induced inflammation and apoptosis in mouse proximal tubular cells
    KM Saad, K Elmasry, B Baban, MJ Livingston, Z Dong, ME Abdelmageed, ...
    International journal of molecular sciences 26 (9), 4115 , 2025
    2025
    Citations: 3
  • Acute nitric oxide synthase inhibition induces greater increases in blood pressure in female versus male Wistar Kyoto rats
    AA Elmarakby, KM Saad, GR Crislip, JC Sullivan
    Physiological reports 11 (15), e15771 , 2023
    2023
    Citations: 3
  • Periodontitis Promotes Brain Aging: Insights from the p16-3MR Senescence Reporter Mouse
    B Crosby, A Carroll, J Williams, K Saad, R Zaman, R El Sayed
    Augusta University , 2026
    2026
  • Obesity Promotes Renal Inflammation and Fibrosis Independent of Sex in SS Leptin Receptor Mutant (SSLepR) Rats
    KM Saad, MS Gad, J Tang, K Capehart, R Abdelsayed, JM Williams, ...
    Biomedicines 13 (1), 3105 , 2025
    2025
  • Maternal Exposure to Tetrahydrocannabinol (THC) During Pregnancy Increases Kidney Damage in Mouse Offspring
    SE Naeini, E Salles, B Bhandari, KM Saad, S Rezaee, AA Elmarakby, ...
    Journal of the American Society of Nephrology 34 (11S), 646 , 2023
    2023
  • Abstract P127: Protective Effects Of Protocatechuic Acid In Murine Model Of UUO-induced Renal Injury
    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