Browsing by Author "Dalkilic, Nizamettin"

Now showing 1 - 5 of 5

Abdominal Ischemia-Reperfusion Induced Cardiac Dysfunction Can Be Prevented by MitoTEMPO
(2021) Akkoca, Ahmet; Celen, Murat Cenk; Tuncer, Seckin; Dalkilic, Nizamettin; 33761811
Background Cardiac dysfunction is secondary to acute mesenteric ischemia (AMI) and abdominal aortic aneurysms (AAA). The underlying cause of distant organ damage in the heart is the formation of oxidative stress caused by ischemia-reperfusion. In this study, we investigated the possible protective effects of a novel mitochondria-targeted antioxidant MitoTEMPO on contractile dysfunction and structural defects of the rat papillary muscle caused by abdominal ischemia-reperfusion (AIR). Methods and Results In the experiments, adult Wistar-Albino rats were used and animals were divided randomly into 3 groups; sham-operated group (SHAM), an IR group that had aortic cross-clamping for 1 h followed by 2 h reperfusion, and a third group that received protective 0.7 mg/kg/day MitoTEMPO injection for 28-day before IR. As a result, it was observed that MitoTEMPO injection had a protective effect on the mechanical activities and structural properties of the papillary muscle impaired by AIR. Our study also showed that AIR disrupted the contractile function of the papillary muscle for each stimulation frequency and post-potentiation responses tested. This is common for each measured and calculated mechanical parameter and MitoTEMPO injection showed its protective effects. Conclusion Consequently, calcium homeostasis seems to be impaired by AIR, and MitoTEMPO may exert its protective effect through energy metabolism by directly targeting the mitochondria.
Can MitoTEMPO protect rat sciatic nerve against ischemia-reperfusion injury?
(2021) Tuncer, Seckin; Akkoca, Ahmet; Celen, Murat Cenk; Dalkilic, Nizamettin; https://orcid.org/0000-0002-2306-4467; 33415504; AAD-6066-2021
Abdominal ischemia-reperfusion (I/R) is known to cause both structural and functional damage to sciatic nerve which is related to the oxidative stress. We investigated the protective effects of mitochondria-targeted antioxidant (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (MitoTEMPO) on ischemia-reperfusion-induced nerve damage by using the conduction velocity distribution (CVD) calculations from in vitro compound nerve action potential (CNAP) recordings from rat sciatic nerve. Adult male Wistar albino rats were divided into three groups. The IR and IR + MT groups had aortic cross-clamping for 1 h followed by 2 h reperfusion, while SHAM group had the same procedure without cross-clamping. IR + MT group received 0.7 mg/kg/day MitoTEMPO injection for 28 days before I/R, while other groups received vehicle alone. Ischemia-reperfusion resulted in a significant decrease (p < .05) in maximum depolarizations (mV), areas (mV.ms), and maximum and minimum upstroke velocities (mV/ms) of CNAPs, while injection of MitoTEMPO showed a complete protective effect on these impairments. The histograms for CVD showed that I/R blocked the contribution of fast-conducting fibers (> 60 m/s). MitoTEMPO prevented that blockage and caused a shift in the CVD. Functional nerve damage caused by I/R can be prevented by MitoTEMPO, which can enter mitochondria, the main source of reactive oxygen species (ROS).
The Effect of MitoTEMPO on Rat Diaphragm Muscle Contraction Parameters in an Experimental Diabetes Model Induced with Streptozotocin
(2023) Akkoca, Ahmet; Tuncer, Seckin; Celen, Murat Cenk; Dalkilic, Nizamettin
Objective: Diabetes Mellitus (DM) not only causes hyperglycemia but also leads to clinical challenges involving respiratory functional impairments. The contraction of the diaphragm reduces pleural pressure, thereby contributing significantly to the process of breathing. This study examines the functional impairments in diaphragm muscle isometric contraction parameters due to increased reactive oxygen species (ROS) associated with DM, as well as the effects of MitoTEMPO, a mitochondria-specific antioxidant, on these impairments. Methods: Wistar Albino male rats at 12-14 weeks of age were randomly divided into three groups: the control group (CON, n=6), the diabetes group (DM, n=6), and the diabetes + MitoTEMPO (MT, n=6) group. A single dose of 50 mg/kg streptozotocin (STZ) was administered to the rats in the DM and MT groups. When the rats in the MT group reached a blood glucose level of 300 mg/dl, they were administered MitoTEMPO at a dose of 0.7 mg/kg/day for 28 days. Isometric contraction recordings were obtained from diaphragm muscle preparations isolated from the experimental animals at the end of the 28-day period. Results: Although the effectiveness of mitochondria-specific antioxidants in reducing blood glucose levels in DM is debated in the literature, results for the MT group were interestingly indicative of a statistically significant decrease in blood glucose levels following MitoTEMPO administration at the end of the fourth week. Furthermore, MitoTEMPO exhibited therapeutic effects on diaphragm muscle contraction parameters impaired by DM. Conclusion: The findings suggest that in DM patients, MitoTEMPO could be utilized for blood glucose control and might also be effective in the treatment of DM-induced diaphragm muscle mechanical dysfunction.
Effects of Oxaliplatin and Cisplatin on Peripheral Nerve Excitability and Conduction
(2021) Burat, Ilksen; Dalkilic, Nizamettin; Tuncer, Seckin
Purpose: This study examines and compares the level of neurotoxicity of oxaliplatin and cisplatin in terms of excitability and conduction parameters over rats' caudal and sciatic nerves. Methods: Twenty-seven Wistar rats were divided into three groups labeled as oxaliplatin (OXA), cisplatin (CIS) and control (CON). OXA and CIS groups were administered oxaliplatin (8 mg/kg/week, i.p) and cisplatin (4 mg/kg/week, i.p) respectively, for a 4.5 week follow-up period. Shortly after, threshold tracking recordings from tail caudal nerve and compound action potential recordings from isolated sciatic nerve were performed, in order to obtain the corresponding excitability and conduction parameters. Results: Cisplatin is found more neurotoxic than oxaliplatin with regards to nerve excitability and conduction. Cisplatin is more effective on fibers having small radius (slowly conducting). The partial blockade of Na+ channels (mostly persistent) and an increment in the activity of inward rectifier K+ conductance due to cisplatin are noteworthy. Conclusions: In terms of neurotoxicity, oxaliplatin may be more preferable compared to cisplatin clinically.
Protective vs. Therapeutic Effects of Mitochondria-Targeted Antioxidant MitoTEMPO on Rat Sciatic Nerve Crush Injury: A Comprehensive Electrophysiological Analysis
(2023) Celen, Murat Cenk; Akkoca, Ahmet; Tuncer, Seckin; Dalkilic, Nizamettin; Ilhan, Barkin; 38137528
Protective vs. Therapeutic Effects of Mitochondria-Targeted Antioxidant MitoTEMPO on Rat Sciatic Nerve Crush Injury: A Comprehensive Electrophysiological Analysis. Peripheral nerve injuries often result in long-lasting functional deficits, prompting the need for effective interventions. MitoTEMPO (2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride) is a mitochondria-targeted antioxidant that has shown protective and therapeutic effects against pathologies associated with reactive oxygen species. This study explores the utilization of MitoTEMPO as a therapeutic and protective agent for sciatic nerve crush injuries. By employing advanced mathematical approaches, the study seeks to comprehensively analyze nerve conduction parameters, nerve excitability, and the distribution of nerve conduction velocities to gauge the potential. Forty Wistar-Albino rats were randomly divided into following groups: (I) SHAM-animals subjected to sham operation and treated intraperitoneally (i.p.) with vehicle (bidistilled water) for 14 days; (II) CI (crush injury)-animals subjected to CI and treated with vehicle 14 days; (III) MiP-animals subjected to 7 days i.p. MitoTEMPO treatment before CI (0.7 mg/kg/day dissolved in vehicle) and, only vehicle for 7 days after CI, protective MitoTEMPO; and (IV) MiT-animals i.p. treated with only vehicle for 7 days before CI and 7 days with MitoTEMPO (0.7 mg/kg/day dissolved in vehicle) after CI, therapeutic MitoTEMPO. Nerve excitability parameters were measured, including rheobase and chronaxie, along with compound action potential (CAP) recordings. Advanced mathematical analyses were applied to CAP recordings to determine nerve conduction velocities and distribution patterns. The study revealed significant differences in nerve excitability parameters between groups. Nerve conduction velocity was notably reduced in the MiP and CI groups, whereas CAP area values were diminished in the MiP and CI groups compared to the MiT group. Furthermore, CAP velocity was lower in the MiP and CI groups, and maximum depolarization values were markedly lower in the MiP and CI groups compared to the SHAM group. The distribution of nerve conduction velocities indicated alterations in the composition of nerve fiber groups following crush injuries. In conclusion, postoperative MitoTEMPO administration demonstrated promising results in mitigating the detrimental effects of nerve crush injuries.