Fakirullahoglu, Mesud; Temiz, Ayetullah; Yeni, Mustafa; Sezgin, Esra Tuba; Yazici, Gulce Naz; Altuner, Durdu; Gulaboglu, Mine; Suleyman, Halis

Background Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor widely used in cancer therapy, has been associated with gastrointestinal adverse effects; however, the underlying mechanisms remain unclear. Previous studies have suggested that oxidative stress may contribute to olaparib-induced tissue injury.Objective This study aimed to investigate the protective effects of adenosine triphosphate (ATP) against olaparib-induced gastric damage in rats.Methods Animals were divided into healthy control (HG), olaparib alone (OLPG), ATP alone (ATPG), and ATP + olaparib (ATOLG) groups. Gastric injury was evaluated by macroscopic assessment of ulcer area and ulcer number. Histopathological alterations were examined using hematoxylin-eosin (H&E) staining, and oxidative stress status was assessed by measuring lipid peroxidation and antioxidant defense parameters.Results Olaparib administration induced marked gastric mucosal injury, characterized by increased ulcer area and ulcer number, severe histopathological damage, and pronounced oxidative stress. In contrast, ATP co-administration significantly attenuated gastric injury, as evidenced by reduced ulcer area and ulcer number, improved histopathological architecture, and restoration of oxidative balance. Compared with the OLPG group, the ATOLG group showed significant improvement in macroscopic, histopathological, and oxidative stress parameters.Conclusion ATP administration attenuated olaparib-induced gastric damage and improved oxidative stress parameters in rats. Although the underlying mechanisms were not directly investigated in the present study, the obtained findings provide preliminary experimental evidence suggesting that ATP may have protective potential against olaparib-induced gastric injury.

Yasar, Yesim Kaya; Sezgin, Esra Tuba; Suleyman, Bahadir; Mammadov, Renad; Ozkaraca, Mustafa; Gungor, Ali; Coban, Taha Abdulkadir; Suleyman, Halis

Background – In this study, the potential protective effects of adenosine triphosphate (ATP) and glutathione (GSH) against atezolizumab-induced cardiac injury in rat heart tissue were investigated. Methods – A total of 24 male albino Wistar rats were used in the experiment. The animals were divided into four groups: healthy group adenosine triphosphate + atezolizumab (ATAZ), GSH + atezolizumab (GHAZ), and atezolizumab alone (ATZ). ATP was administered intraperitoneally at a dose of 4 mg/kg, while GSH was administered orally at a dose of 200 mg/kg for 7 days. Atezolizumab was administered intraperitoneally to the experimental groups at a dose of 10 mg/kg twice weekly. At the end of the experiment, malondialdehyde total glutathione (tGSH), superoxide dismutase catalase, interleukin-1β (IL-1β), and interleukin-6 (IL-6) levels in heart tissues were measured using biochemical methods. In addition, histopathological and immunofluorescence examinations were performed. Results – The results showed that oxidative stress and inflammation markers increased, whereas antioxidant parameters decreased in the atezolizumab-treated group. ATP and GSH administration significantly attenuated these changes and exerted protective effects on cardiac tissue. Conclusion – Overall, ATP and GSH ameliorated the biochemical, histopathological, and immunofluorescence changes associated with atezolizumab-induced cardiac injury in this experimental model.

Gozen, Fusun; Sezgin, Esra Tuba; Yavuzer, Bulent; Sarigul, Cengiz; Mammadov, Renad; Suleyman, Bahadir; Altuner, Durdu; Suleyman, Halis

Introduction – Propofol is a short-acting intravenous hypnotic anesthetic widely used for sedation and the induction and maintenance of general anesthesia. Although it reliably produces unconsciousness, its intrinsic analgesic efficacy remains a subject of debate. Accumulating evidence indicates that propofol suppresses catecholaminergic activity, and inhibition of endogenous adrenaline may therefore limit its ability to modulate nociceptive processing. Accordingly, this study aimed to investigate the nociceptive suppressions of subhypnotic and anesthetic doses of propofol in rats and their relationship with endogenous adrenaline levels. Methods – Thirty-six male Wistar rats were randomly allocated into six experimental groups: healthy healthy control, subhypnotic-dose propofol (25 mg/kg; PRO-25, intraperitoneally), anesthetic-dose propofol (50 mg/kg; PRO-50, intraperitoneally), adrenaline-alone (0.3 mg/kg; ADRG, intraperitoneally), and adrenaline combined with subhypnotic or anesthetic-dose propofol (PRAD-25 and PRAD-50). Mechanical paw withdrawal thresholds, anesthetic duration, behavioral responses to standardized scalpel incision, and plasma adrenaline levels were evaluated using statistical analyses. Results – Propofol administered alone failed to produce significant nociceptive suppressionat either dose and induced dose-dependent suppression of circulating adrenaline, whereas adrenaline alone exerted no significant effect on nociceptive thresholds. In contrast, combined administration significantly increased pain thresholds at subhypnotic doses and abolished responses to surgical incision at anesthetic doses despite comparable anesthetic duration. Notably, co-administration restored serum adrenaline levels toward physiological values at lower, but not higher, propofol doses. Conclusion – These findings provide experimental results suggesting that nociceptive responses observed during propofol exposure may be modulated by endogenous adrenergic activity. This interaction may contribute to explaining the dissociation between anesthetic depth and nociceptive suppression and points to a catecholaminergic influence on anesthetic–nociceptive dynamics that has not been sufficiently investigated previously.

Kozan, Günay; Üstündağ, Hilal; Kara, Adem

Background – Polystyrene nanoplastics (NPs) represent emerging environmental contaminants with potential adverse effects on salivary glands. This study investigated the protective effects of multi-strain probiotics against NPs-induced toxicity in rat parotid glands. Methods – Forty male Sprague-Dawley rats were allocated into five groups (n = 8): control, NPs (10 mg/kg), probiotics (1010 CFU), NPs + probiotics low dose (109 CFU), and NPs + Pro high dose (1010 CFU). Treatments were administered orally for 35 days. Oxidative stress markers, histopathological changes, and protein expression were evaluated. Results – NPs exposure significantly increased MDA levels (p < 0.05) and decreased SOD activity and GSH content (p < 0.05). Histopathological examination revealed moderate to severe acinar degeneration (++) and fibrosis (++) in NPs-treated animals. Western blot analysis showed significant downregulation of Bcl-2 (p < 0.01), HO-1 (p < 0.0001), NRF2 (p < 0.01), and AQP5 (p < 0.0001), with upregulation of Caspase-3 (p < 0.0001), NF-κB (p < 0.001), IL-1β (p < 0.001), and TNF-α (p < 0.001). Probiotic supplementation significantly ameliorated oxidative stress (p < 0.05), reduced histopathological damage to mild changes (+), and restored beneficial protein expression while suppressing inflammatory markers (p < 0.01-0.001). Conclusion – This study provides the first evidence that NPs induce significant oxidative stress and tissue damage in parotid glands. Multi-strain probiotics provide substantial protection by activating the NRF2/HO-1 pathway and suppressing inflammation, suggesting a promising therapeutic strategy against nanoplastic-induced oral tissue damage.

Kilic, Adil Furkan; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Mendil, Ali Sefa; Suleyman, Halis

Aim – Trans-ferulic acid (TFA), a naturally occurring phenolic compound, has attracted significant attention due to its strong hepatoprotective and neuroprotective properties. Despite extensive research on its overall biological activities, the specific mechanisms by which TFA influences hepatic encephalopathy (HE) remain unclear. This study aims to explore the therapeutic potential of TFA by examining its effects on inflammatory signaling, glial activation, and apoptotic pathways in a thioacetamide (TAA)-induced rat model of HE. Methods – Rats were separated into four groups: a normal control group, the TAA group (which received TAA at 300 mg/kg/day for 3 days), and groups pre-treated with TFA (at doses of 25/50 mg/kg, administered orally) for 10 days, with TAA administered from the eighth to the 10th day. Results – TFA pre-treatment effectively reduced TAA-induced biochemical disturbances, as shown by lower serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and ammonia. This biochemical improvement was complemented by a significant reduction in TAA-related hepatic histopathological damage. TFA also alleviated systemic inflammation by suppressing TAA-induced increases in pro-inflammatory mediators, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), while also elevating the anti-inflammatory cytokine IL-10. Consistent with these results, TFA further suppressed the activation of MAPK/NF-κB inflammatory signaling pathways in both liver and brain tissues and decreased glial fibrillary acidic protein (GFAP) expression in the brains of TAA-treated rats, indicating reduced neuroinflammation and astrocyte activation. Additionally, immunochemical analysis showed that TFA pre-treatment effectively prevented the TAA-induced increase in pro-apoptotic markers Caspase-3 and Bax in both liver and brain tissues. This study underscores the strong protective effects of TFA against TAA-induced HE, mainly through inhibition of MAPK/NF-κB signaling, suppression of astrocyte activation, and reduction of apoptosis. Conclusion – These outcomes imply that TFA could be an effective treatment for HE.

Karadogan, Muhammed Talha; Cicek, Betul; Cinisli, Kagan Tolga; Mendil, Ali Sefa; Ozkaraca, Mustafa; Yilmaz, Furkan; Suleyman, Halis

Introduction: Doxorubicin (DOX) is a potent anti-neoplastic agent widely preferred in treating various tumors. However, DOX’s off-target toxicity in healthy tissues, such as nephrotoxicity, limits its clinical utilization. DOX generates oxidative stress and apoptosis in the kidneys, which stimulates cytotoxic cellular signaling. Myricetin (MYC), an important natural flavonoid, exhibits antioxidant and antiapoptotic features. In this regard, the current report was designed to explore the renoprotective potential of MYC on DOX-induced nephrotoxicity. Methods: Animals were divided into four groups with six rats in each group: control, MYC, DOX, MYC + DOX. MYC was given orally to rats at 100 mg/kg for 10 days and DOX was injected intraperitoneally as a single dose of 20 mg/kg on the eighth day. Serum samples were evaluated for creatinine and blood urea nitrogen (BUN), and histopathological analysis of the kidneys was conducted. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), total oxidant status (TOS), glutathione (GSH), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) were measured in the renal tissues. Additionally, biochemical assessments of Bax and Bcl-2 proteins, along with immunohistochemical evaluations of the expression levels of caspase-3 and apoptosis-inducing factor (AIF), were conducted to evaluate apoptosis. Results: Pre-treatment of MYC decreased DOX-elicited elevation in creatinine and BUN levels (p < 0.05). Histopathological findings demonstrated the nephroprotective role of MYC on renal damage (p < 0.05), which was in harmony with the biochemical findings. Furthermore, MYC demonstrated antioxidant properties by reversing the increase in MDA, TOS, and MPO levels and the decrease in GSH, GPx, and TAS levels caused by DOX (p < 0.05). MYC pre-treatment also markedly prohibited DOX-induced elevation of Bax level, and rise of expression of caspase-3 and AIF, and reduction of Bcl-2 levels (p < 0.05). Conclusion: It could be supposed that the nephroprotective role of MYC towards DOX-induced kidney damage might be mediated by its antioxidant and antiapoptotic features.

Isik, Bahar; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Yavuzer, Bulent; Altuner, Durdu; Coban, Taha Abdulkadir; Suleyman, Halis

Background: The role of oxidative stress and inflammation in cobalt (Co) toxicity has been the focus of previous studies. Cinnamon and its main components have been reported to have protective effects in various tissues with antioxidant and anti-inflammatory effects. Aims: In this study, the protective effect of cinnamon extract (CE) against possible Co-induced heart, kidney, and liver damage in rats was investigated biochemically. Methods: Eighteen albino Wistar-type male rats were categorized into three groups (n = 6 per group): control (CG), CoCL2-administered (CoCL2), and CE + CoCL2-administered (CE + Co) groups. The CE + CoCL2 group was administered CE (100 mg/kg), and the CoCL2 and CG groups were administered distilled water orally by gavage. One hour after the administration, Co (150 mg/kg) was administered orally to the CE + CoCL2 and CoCL2 groups. This procedure was repeated once daily for 7 days. Then, biochemical markers were studied in the excised heart, kidney, and liver tissues. Results: CoCL2 increased oxidants and proinflammatory cytokines and decreased antioxidants in heart, kidney, and liver tissues. Heart, kidney, and liver tissue were affected by Co damage. CE treatment suppressed the CoCL2-induced increase in oxidants and proinflammatory cytokines and decrease in antioxidants in heart, kidney, and liver tissues. CE treatment has been shown to attenuate cardiac damage by reducing serum troponin I (TpI) and creatine kinase-MB (CK-MB), renal damage by reducing creatinine and blood urea nitrogen (BUN), and liver damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Conclusion: Co induced the production of oxidants and proinflammatory parameters and antioxidant depletion in heart, kidney, and liver tissues of rats. Our experimental results show that CE protects heart, kidney, and liver tissues against oxidative and inflammatory changes induced by CoCLl2.

Emir, Izzet; Bulut, Seval; Suleyman, Bahadır; Mammadov, Renad; Yucel, Nurinisa; Cicek, Betul; Yazici, Gulce Naz; Altuner, Durdu; Gunay, Murat; Suleyman, Halis

Aim: The current study aimed to investigate the protective effects of adenosine triphosphate (ATP), metyrosine, and melatonin on possible methylphenidate cardiotoxicity in rats using biochemical and histopathological methods. Methods: Thirty rats were separated into five groups: healthy (HG), methylphenidate (MP), ATP + methylphenidate (ATMP), metyrosine + methylphenidate (MSMP), and melatonin + methylphenidate (MLMP). ATP (5 mg/kg) was given intraperitoneally once daily, metyrosine (50 mg/kg) orally twice daily, and melatonin (10 mg/kg) orally once daily. Methylphenidate (10 mg/kg) was administered orally once daily for 1 h after ATP, metyrosine and melatonin. The protocol was repeated for 30 days. Subsequently, blood samples were taken from the tail veins of the animals to measure adrenaline, noradrenaline, dopamine, troponin I (TP I) and creatine kinase MB (CK-MB) levels; the animals were then euthanized and the heart tissues were extracted. Tissues were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) and histopathologically. Results: In MP group, MDA, adrenaline, noradrenaline, dopamine, TP I, and CK-MB levels increased (p < 0.001) and tGSH, SOD, and CAT levels decreased (p < 0.001) compared to HG, and histopathologic damage developed. Oxidant levels were lower and antioxidant levels were higher in ATMP, MSMP, and MLMP groups compared to MP group (p < 0.001). Catecholamine levels were measured lower in the MSMP group compared to the MP group (p < 0.001). TP I and CK-MB levels were lower in ATMP, MSMP and MLMP groups compared to MP (p < 0.05), with the lowest being in rats given ATP (p < 0.001). ATP, melatonin, and metirozin applications were effective to different degrees in preventing histopathological changes. Conclusion: This study may guide clinical trials using ATP and melatonin to prevent methylphenidate-induced myocardial injury.

Cerrah, Serkan; Ozcicek, Fatih; Gundogdu, Betul; Cicek, Betul; Coban, Taha Abdulkadir; Suleyman, Bahadir; Altuner, Durdu; Bulut, Seval; Suleyman, Halis

Background: Acrylamide causes hepatotoxicity with the effect of oxidative stress and inflammatory processes. Carvacrol is a monoterpenic phenol with antioxidant and anti-inflammatory properties. Aims: To determine the effects of carvacrol on oxidative liver injury induced by acrylamide administration in rats. Methods: Rats were divided into three groups of six animals each: healthy group acrylamide group (ACR), and acrylamide + carvacrol group (TACR). First, carvacrol (50 mg/kg) was administered intraperitoneally to the CACR group. One hour later, acrylamide (20 mg/kg) was given orally to the ACR and CACR groups. This procedure was performed for 30 days, after which the animals were sacrificed. The malondialdehyde (MDA) and total glutathione (tGSH) levels, total oxidant (TOS) and total antioxidant status (TAS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and nuclear factor kappa b (NF-κB) were measured in the excised liver tissues. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined in blood serum samples. Liver tissues were also examined histopathologically. Results: In the ACR group, malondialdehyde, TOS, ALT, AST levels, and NF-κB, IL-1β, and TNF-α levels were found to be high, and tGSH and total antioxidant status levels were low. In addition, diffuse degenerative changes and necrosis in hepatocytes, and moderate inflammation in the portal region were detected in the liver tissues of the ACR group. While carvacrol prevented the biochemical changes induced by acrylamide, it also alleviated the damage in the histological structure. Conclusion: Carvacrol may be used for liver damage caused by acrylamide.

Bedir, Zehra; Ozkaloglu Erdem, Kezban Tuna; Doymus, Omer; Suleyman, Halis; Yavuzer, Bulent; Cicek, Betul; Altuner, Durdu; Mammadov, Renad; Yilmaz, Mehmet; Coban, Taha Abdulkadir

Introduction: In clinical practice, inadequate pain inhibition leads to increased morbidity and mortality. Increased intracellular calcium, oxidants, and proinflammatory cytokines are known to play a role in the pathogenesis of postoperative pain. Therefore, we investigated the analgesic effects of benidipine, paracetamol, and benidipine-paracetamol combination (BPC) on postoperative and normal pain thresholds in rats. Material and methods: Sixty-four male albino Wistar rats weighing 285–295 g were used. The without-incision rats were divided into 4 subgroups: healthy control, benidipine alone, paracetamol alone, and BPC. The scalpel-incision rats were divided into 4 subgroups: scalpel incision, scalpel incision + benidipine, scalpel incision + paracetamol, and scalpel incision + BPC. Paw pain thresholds of rats were measured using a Basile algesimeter. Biochemical analyses were performed on the paw tissues of 6 rats randomly taken from the experimental groups, each containing 8 rats. Rats were sacrificed immediately after the measurements. After the pain threshold tests were finished, the paw tissues were removed and malondialdehyde (MDA), total glutathione (tGSH), cyclooxygenase (COX), and interleukin-6 (IL-6) levels were measured. Results: There was no significant difference between the groups in paw pain threshold and measured biochemical parameters in rats without incision. The decrease in the pain threshold of the incised paw was also best prevented by BPC, followed by benidipine and then paracetamol. Furthermore, increases in scalpel-incised paw tissue MDA, COX-2, and IL-6 levels and the decrease in tGSH were significantly suppressed by benidipine and BPC, while paracetamol could only significantly inhibit the increase in IL-6 production. Conclusion: The combination of the L-type Ca2+ channel blocker benidipine and paracetamol (BPC) may provide potent analgesia. Our experimental results support that BPC may be useful in the treatment of severe pain that cannot be adequately inhibited by paracetamol.