Plasma neurological biomarkers as a measure of neurotoxicity in pediatric dental general anesthesia: a prospective observational feasibility study.

PURPOSE: Neurotoxicity concerns have been raised over general anesthesia and sedation medication use in children. Such concerns are largely based on animal studies, historical anesthetic agents, and assessment tools, thus warranting further investigations. Blood biomarkers in detecting neuronal inflammation and apoptosis are novel methods for detecting neuronal damage. Therefore, the aim of this feasibility study was to assess the usefulness of the levels of four plasma biomarkers in dental general anesthesia (DGA) as surrogate markers of neurotoxicity in children. The secondary aim was to compare changes in motor manipulative skills pre- and post-anesthetic exposure. METHODS: This single-center prospective observational study included 22 healthy children aged between 3 and 6 years old who underwent DGA. Subclinical neurotoxicity was measured with a panel of four plasma biomarkers: Caspase-3, neuron-specific enolase (NSE), neurofilament light chain, and S100B at three time points (1; at start, 2; end and 3; on recovery from DGA). The Skillings-Mack test was used to identify the difference in the biomarker levels at three time points. Motor manipulative score assessment, prior and two weeks after DGA was also performed. RESULTS: A total of 22 study participants (mean age = 5 ± 1 years) were included with a median DGA duration of 106 ± 28 min. A reduction in Caspase-3 levels was recorded, with pairwise comparison over three time points, reporting a statistical significance between time point 2 vs. 1 and time point 3 vs. 1. Although fluctuations in NSE levels were recorded, no significant changes were found following pairwise comparison analysis. Among other biomarkers, no significant changes over the three periods were recorded. Furthermore, no significant changes in manipulative motor scores were reported. CONCLUSION: Caspase-3 reduced significantly in the short time frames during day-care DGA; this might be due to the relatively short anesthesia duration associated with dental treatment as compared with more extensive medical-related treatments. Therefore, further studies on Caspase-3 as a potential biomarker in pediatric DGA neurotoxicity are required to further ascertain results of this study.

The effects of the exposure to neurotoxic elements on Italian schoolchildren behavior.

Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency's priority list of hazardous substances where arsenic and lead are ranked as first and second respectively.

Neuroglobin alleviates arsenic-induced neuronal damage.

People who drink water contaminated with arsenic for a long time develop neuritis, cerebellar symptoms, and deficits in memory and intellectual function. Arsenic induces oxidative stress and promotes apoptosis through multiple signalling pathways in nerve cells. Neuroglobin (Ngb), as a key mediator, is considered to be protective against oxidative stress. In this study, we aimed to study the effects of Ngb knockdown in arsenite-treated rat neurons on levels of apoptosis markers and reactive oxygen species and serum Ngb levels of subjects from arsenic-endemic regions in China. We discovered that arsenic-induced apoptosis and reactive oxygen species production were enhanced in Ngb-knocked-down rat neurons. Silencing of Ngb aggravated the arsenic-induced decrease in the rate of Bcl-2/Bax and the levels of Bcl-2 protein following arsenite treatment. The results also showed that serum Ngb levels were independently negatively correlated with arsenic concentration in drinking water. Furthermore, the serum Ngb levels of four groups (245 individuals) according to different degree exposure to arsenic were 815.18 ± 89.52, 1247.97 ± 117.18, 774.79 ± 91.55, and 482.72 ± 49.30 pg/mL, respectively. Taken together, it can be deduced that Ngb has protective effects against arsenic-induced apoptosis by eliminating reactive oxygen species.

Potential Role of Serum S-100ß Protein as a Predictor of Cardiotoxicity and Clinical Poor Outcome in Acute Amphetamine Intoxication.

Cardio- and neurotoxicity of amphetamines play an important role in worsening morbidity, making the initial evaluation of the patient's status a potentially lifesaving action. The current study hypothesized that the S-100ß serum level could predict the severity of acute amphetamine toxicity and the in-hospital outcome. The current study is a prospective cohort study conducted on 77 patients diagnosed with acute amphetamine exposure and referred to Aseer Poison Control Center, Saudi Arabia. The patients admitted to ICU showed significantly higher serum levels of S-100ß in comparison to those not admitted (p < 0.05). Moreover, the S-100ß level was significantly elevated among patients with prolonged QTc intervals. Receiver-operating characteristic curve of S-100ß serum level as an in-hospital outcome predictor showed that at a cutoff value > 0.430 ug/L, the sensitivity of S-100ß serum level as severity predictor was 100%, and the specificity was 74.1%. In conclusion, the current study revealed that the S-100ß serum level could be used as an outcome predictor in hospital admission cases due to toxic amphetamine exposure and offers an idea about the cardiac and neuronal involvement. This can help select patients who will benefit most from ICU admission and early management and assess the severity of cases in settings where GC-MS is not available.

Neurotoxicity after hematopoietic stem cell transplant in multiple sclerosis.

OBJECTIVE: Accelerated brain volume loss has been noted following immunoablative autologous hematopoietic stem cell transplantation (IAHSCT) for multiple sclerosis. As with other MS treatments, this is often interpreted as 'pseudoatrophy', related to reduced inflammation. Treatment-related neurotoxicity may be contributory. We sought objective evidence of post-IAHSCT toxicity by quantifying levels of Neurofilament Light Chain (sNfL) and Glial Fibrillary Acidic Protein (sGFAP) before and after treatment as markers of neuroaxonal and glial cell damage. METHODS: Sera were collected from 22 MS patients pre- and post-IAHSCT at 3, 6, 9, and 12 months along with 28 noninflammatory controls. sNfL and sGFAP quantification was performed using the SiMoA single-molecule assay. RESULTS: Pre-IAHSCT levels of sNfL and sGFAP were elevated in MS patients compared with controls (geometric mean sNfL 21.8 vs. 6.4 pg/mL, sGFAP 107.4 vs. 50.7 pg/mL, P = 0.0001 for both). Three months after IAHSCT, levels of sNfL and sGFAP increased from baseline by 32.1% and 74.8%, respectively (P = 0.0029 and 0.0004). sNfL increases correlated with total busulfan dose (P = 0.034), EDSS score worsening at 6 months (P = 0.041), and MRI grey matter volume loss at 6 months (P = 0.0023). Subsequent NfL levels reduced to less than baseline (12-month geometric mean 11.3 pg/mL P = 0.0001) but were still higher than controls (P = 0.0001). sGFAP levels reduced more slowly but at 12 months were approaching baseline levels (130.7 pg/mL). INTERPRETATION: There is direct evidence of transient CNS toxicity immediately after IAHSCT which may be chemotherapy mediated and contributes to transient increases in MRI atrophy.

Neurofilament light chain: a specific serum biomarker of axonal damage severity in rat models of Chemotherapy-Induced Peripheral Neurotoxicity.

Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a severe and long-lasting side effect of anticancer therapy, which can severely impair patients' quality of life. It is a sensory and length-dependent neuropathy, which predominantly affects large myelinated fibers. Easy and reliable monitoring of CIPN in patients is still an unmet clinical need. Since increasing clinical evidence supports the potential use of neurofilament light chain (NfL) as a biomarker of axonal injury, in this study we measured serum NfL levels in animals chronically treated with cisplatin (CDDP) and paclitaxel (PTX), two antineoplastic drugs with different neuronal targets. Wistar rats were treated with CDDP (2 mg/kg i.p. twice/week for 4 weeks) or PTX (10 mg/kg i.v. once/week for 4 weeks). Repeated serum NfL quantification was obtained using the Single Molecule Array (Simoa) technology. The onset and progression of peripheral neurotoxicity were evaluated through neurophysiology, morphological assessments and intraepidermal nerve fibers density quantification. Our results showed that serum NfL measurements correlated with the severity of axonal damage. In fact, both treatments induced serum NfL increase, but higher levels were evidenced in PTX-treated animals, compared with CDDP-treated rats, affected by a milder neurotoxicity. Notably, also the timing of the NfL level increase was associated with the severity of morphological and functional alterations of axonal structure. Therefore, NfL could be a useful biomarker for axonal damage in order to follow the onset and severity of axonal degeneration and possibly limit the occurrence of serious PNS disease.

High ambient temperature increases the toxicity and lethality of 3,4-methylenedioxymethamphetamine and methcathinone.

RATIONALE: Methylenedioxymethamphetamine (MDMA) and methcathinone (MCAT) are abused psychostimulant drugs that produce adverse effects in human users that include hepatotoxicity and death. Recent work has suggested a connection between hepatotoxicity, elevations in plasma ammonia, and brain glutamate function for methamphetamine (METH)-induced neurotoxicity. OBJECTIVES: These experiments investigated the effect of ambient temperature on the toxicity and lethality produced by MDMA and MCAT in mice, and whether these effects might involve similar mechanisms to those described for METH neurotoxicity. RESULTS: Under low (room temperature) ambient temperature conditions, MDMA induced hepatotoxicity, elevated plasma ammonia levels, and induced lethality. Under the same conditions, even a very high dose of MCAT produced limited toxic or lethal effects. High ambient temperature conditions potentiated the toxic and lethal effects of both MDMA and MCAT. CONCLUSION: These studies suggest that hepatotoxicity, plasma ammonia, and brain glutamate function are involved in MDMA-induced lethality, as has been shown for METH neurotoxicity. The toxicity and lethality of both MDMA and MCAT were potentiated by high ambient temperatures. Although an initial mouse study reported that several cathinones were much less toxic than METH or MDMA, the present results suggest that it will be essential to assess the potential dangers posed by these drugs under high ambient temperatures.

Identification of markers of depression and neurotoxicity in pesticide exposed agriculture workers.

Earlier, we reported that chronic exposure to pesticides causes a reduction in the acetylcholinesterase activity and hematological and biochemical alterations in agriculture workers. In continuation with that, the present study aimed to investigate the pesticide-induced neurochemical imbalance and its association with behavior alterations in agricultural workers. A significant increase in depressive symptoms, assessed by the Beck Depression Inventory-II was observed in pesticide exposed workers as compared to the unexposed. A decrease in the level of dopamine in plasma and levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acids, norepinephrine, serotonin, and hydroxyindoleacetic acid in urine was also observed. An increase in the levels of MAO-A and MAO-B has also been observed in these individuals. The decreased levels of neurotransmitters in the blood and urine have been linked with increased levels of MAO and pesticide residues in plasma and urine. Furthermore, these changes were associated with a higher incidence of depression in agricultural workers.

Carbon monoxide intoxication in geriatric patients: How important are lactate values at admission?

PURPOSE: The aim of this study was to investigate the demographic and clinical characteristics and treatment modalities of elderly patients with carbon monoxide (CO) intoxication. The secondary aim was to evaluate the importance of plasma lactate values in the diagnosis of acute CO intoxication in geriatric patients. METHODS: Data on geriatric patients who were admitted to the emergency department of Atatürk University Medical Faculty between January 2013 and April 2016 were analyzed retrospectively. RESULTS: Of the 197 cases included in the study, 97 were in the intoxication group and 100 were in the control group; 82.5% of the intoxication cases had mild neurological symptoms and 17.5% had severe neurological symptoms. Carboxyhemoglobin levels were significantly higher in patients with severe neurological symptoms (p = 0.031). All patients with severe neurological symptoms received hyperbaric-oxygen therapy (p < 0.001). In the intoxication group, lactate levels were significantly higher than in the control group (p = 0.001). The specificity for lactate 4 mmol/L and above was found as 98.0% with a positive predictive value and negative predictive value of 84.5% and 53.3%, respectively. CONCLUSION: High initial lactate levels may be a guide for cases with nonspecific symptoms in geriatric patients with suspected CO intoxication.

Thiamine deficiency and oxidative stress induced by prolonged metronidazole therapy can explain its side effects of neurotoxicity and infertility in experimental animals: Effect of grapefruit co-therapy.

We aimed to explore the possible neurotoxicity and infertility mechanisms of prolonged metronidazole (MTZ) use and the effects of antioxidant grapefruit (GP) co-therapy on MTZ-induced complications. Sixty male albino Wistar rats were divided into four groups (n = 15 each). Group I (control group) received 1% dimethyl sulfoxide (27 ml/ kg/day), group II (MTZ group) received MTZ (400 mg/kg/day), group III (MTZ + GP) received MTZ (400 mg/kg/ day) plus GP juice (27 ml/kg/ day) and group IV (GP group) received GP juice (27 ml/kg) for 60 days. Semen analyses were performed. Free testosterone, gonadotrophin (follicle-stimulating hormone (FSH) and luteinizing hormone) and thiamine levels were measured. Samples of cerebellar, testicular and epididymal tissues were used for both colorimetric assays of oxidative stress markers and histopathological examinations. Significant decreases in the sperm count, percent total sperm motility, serum thiamine levels, free testosterone levels and FSH levels were observed in the MTZ and MTZ + GP groups (p < 0.05 for all parameters). Significantly higher oxidative stress levels (p < 0.05) were observed in the cerebellar and testicular tissue homogenates of these groups than in those of the control group, and associated disruptions in the cerebellar, testicular and epididymal structures were apparent compared to those of the control group. Although the GP group showed a significantly higher sperm count and significantly lower oxidative stress than the control group (p < 0.05), with histological similarity to the control group, the GP group exhibited significantly higher prolactin levels and lower free testosterone and FSH levels than the control group (p < 0.05). Oxidative stress and decreased thiamine levels could explain the MTZ-induced neurotoxicity and infertility side effects that aggravated by GP co-administration.

S-100ß in predicting the need of hyperbaric oxygen in CO-induced delayed neurological sequels.

BACKGROUND: Delayed neurological sequels (DNS) have been described after carbon monoxide (CO) poisoning. There is a need to find a new prognostic marker to guide the use of hyperbaric oxygen (HBO) therapy. AIM: To evaluate serum S-100ß level in patients presenting with acute CO poisoning as an indicator of poisoning severity and predictor of DNS occurrence and HBO need in those patients. METHODS: This prospective cohort study included patients with acute CO poisoning. On admission, carboxyhemoglobin (COHb) and S-100ß levels were measured. Patients were followed up for 6 months for signs of DNS. RESULTS: Out of 50 patients, 6 only developed DNS. The mean of S-100ß levels was significantly higher in patients with severe poisoning and those with DNS. Receiver operating characteristic curve analysis revealed that S-100ß had an area under the curve 0. 871; at a cutoff value ≥ 0.67 µg/L, its sensitivity and specificity were 100% and 77.3%, respectively. The sensitivity of S-100ß was significantly higher than that of COHb, while its specificity and overall accuracy were significantly higher than those of HBO criteria. CONCLUSION: Serum S-100ß level on admission could be a marker of poisoning severity and a predictor of CO-induced DNS development that guides the use of HBO therapy.

Elevated Lipase in an Infant with Altered Mental Status.

The pancreatic enzymes lipase and amylase serve important functions in digestion/absorption of fats and polysaccharides. Measurement of these enzymes is often used in the emergency department to rule out acute pancreatitis in patients with nonspecific abdominal pain. In acute pancreatitis, serial measurements of plasma lipase and amylase typically follow a predictable temporal pattern of rise-and-fall kinetics: lipase levels rise within 4 to 8 hours, crest at 2× to 50× the upper reference limit at 24 hours, and decline to normal concentrations in 7 to 14 days. In situations in which the duration and magnitude of pancreatic enzyme elevation are more transient, clinicians should consider alternative causes for enzyme elevation. In this case report, incidental discovery of elevated lipase in an African American baby girl who ingested oxycodone resulted in additional laboratory and radiological work-up. Stronger awareness of exogenous influences on gastrointestinal motility may have prevented the need for further testing in this patient.

Predictive value of plasma neutrophil gelatinase-associated lipocalin in acute charcoal-burning carbon monoxide poisoning.

This study aimed to assess the feasibility of using the plasma neutrophil gelatinase-associated lipocalin (NGAL) level at the time of presentation in the emergency department (ED) to predict acute kidney injury (AKI) and the long-term neurological outcomes of acute charcoal-burning carbon monoxide (CO) poisoning. This retrospective study included 260 patients who suffered acute charcoal-burning CO poisoning. The median plasma NGAL concentration at the time of presentation in the ED after acute charcoal-burning CO poisoning was 78 (54-115) ng/ml. The NGAL level was an independent predictor of AKI development and could be used to stratify the severity of AKI. However, the area under the receiver operating characteristic curve (AUC) of the predictive model for AKI that included both the plasma NGAL level and clinical parameters was comparable to that of the predictive model including only the clinical parameters. The plasma NGAL level at the time of presentation in the ED was an independent factor predicting long-term neurological outcomes in patients who did not develop AKI. In these patients, the plasma NGAL level significantly improved the predictive accuracy of the model when used in combination with clinical parameters. In contrast, the plasma NGAL level was not associated with long-term neurological outcomes in patients who developed AKI. Measurement of the plasma NGAL level at the time ED presentation might improve the prediction of long-term neurological outcomes in patients who do not develop AKI after acute charcoal-burning CO poisoning. However, it might not offer additional benefit for AKI prediction compared to previously used markers.

Bismuth Concentrations in Patients Treated in Real-Life Practice with a Bismuth Subcitrate-Metronidazole-Tetracycline Preparation: The SAPHARY Study.

INTRODUCTION: A fixed-dose association of bismuth subcitrate, metronidazole and tetracycline (BMT) (Pylera®, Allergan, NJ, USA) was made available in France in 2013 for the eradication of Helicobacter pylori. Due to a historical issue of bismuth encephalopathy, the French Health Authorities requested a study of blood and plasma bismuth concentrations with BMT in daily practice. AIMS: The aim of the study was to measure eventual bismuth accumulation and neurological toxicity in patients prescribed BMT. METHODS: Patients initiating BMT for H. pylori between March 2014 and December 2015 were included. A blood sample was taken before first BMT intake and 24 h after the last intake, for assay of bismuth. A concentration > 50 µg/L was considered abnormal. Neurological complaints were assessed at inclusion, at the end of the 10-day treatment course, and 28 days later. RESULTS: 202 patients were included, of whom 190 took at least one dose of BMT, and 167 provided both required blood samples. Mean blood bismuth concentrations after the BMT course were 16.9 µg/L (95% confidence interval 15.6-18.3). Concentrations were > 50 µg/L (56.0 µg/L and 50.9 µg/L) in two elderly patients, one of whom presented mild, transient memory impairment during treatment. Non-serious neurological symptoms occurred in 20% of all patients and treatment failure was documented in 5% of patients. CONCLUSIONS: In this study measuring blood bismuth concentrations in real-life practice, in < 1% of patients the BMT course resulted in blood bismuth concentrations > 50 µg/L. No serious neurological adverse events were observed. STUDY REGISTRATION: EU-PAS register EUPAS3142 at www.encepp.eu ; ENCePP study seal.

Comparison of the neurotoxicity associated with cobalt nanoparticles and cobalt chloride in Wistar rats.

Cobalt nanoparticles (CoNPs) have been widely used in industry given their physical, chemical and magnetic properties; however, CoNPs may cause neurological symptoms and diseases in human, yet their mechanisms of toxicity remain unknown. Here, we used male Wistar rats to investigate differences in the toxic effects associated with CoNPs and CoCl2. Upon exposure to CoCl2, and 96 nm or 123 nm CoNPs at the same concentration, the Co2+ content in CoCl2 group was significantly higher than that in either the CoNPs groups in brain tissues and blood, but lower in liver. Significant neural damage was observed in both hippocampus and cortex of the temporal lobe. Increase malondialdehyde (MDA) content and CASPASE 9 protein level were associated both with CoCl2 and CoNPs treatments, consistent with lipid perioxidation and apoptosis. Heme oxygenase-1 and (NF-E2) p45-related factor-2 protein levels were elevated in response to 96 nm CoNPs exposure. In PC12 cells, NRF2 downregulation led to reduced cell viability and increased apoptotic rate. In conclusion, both CoNPs and CoCl2 cause adverse neural effects, with nanoparticles showing greater neurotoxic potency. In addition, NRF2 protects neural cells from damage induced by CoCl2 and CoNPs by activating downstream antioxidant responses.

Determination of netrin-1 levels and its relationship with neurotoxicity in carbon monoxide poisoning.

OBJECTIVE: The aim of the study was to assess netrin-1 levels in carbon monoxide (CO) poisoning to determine its relationship with poisoning severity and neurotoxicity. METHODS: This is a cross-sectional prospective study. The patients older than 18 years with CO poisoning were included. The patients were categorized into two groups on the basis of neurological involvement. Both the patient and the control groups were sampled for netrin-1 at 0th hour, and the patient group only was sampled for netrin-1 at 4th hour. RESULTS: A total of 84 patients and 50 healthy controls were enrolled. The median 0th hour netrin-1 level of the patient group (765.1 pg/mL (619.8-983.1) was significantly higher than the control group (484 pg/mL (376-1031.6)) ( p < 0.001). There was also a significant difference between the 0th hour and 4th hour netrin-1 (888.9 pg/mL (700.3-1175.5)) levels in the patient group ( p < 0.001).There was no significant statistical difference between patients with and without neurological involvement ( p = 0.62) and between those who underwent hyperbaric oxygen therapy (HBOT) and those who did not ( p = 0.76) with respect to 4th hour netrin-1 levels. CONCLUSION: The significantly higher netrin-1 levels in patients with CO poisoning, suggests that netrin-1 is elevated as a stress marker. Although there is no significant difference in netrin-1 levels in patients with neurological impairment in CO poisonings, netrin-1 may show subclinically neurological effects. Hence, we believe that netrin-1 cannot be used as a marker of poisoning severity.

Serum lactate as a predictor of neurologic outcome in ED patients with acute carbon monoxide poisoning.

BACKGROUND: This study was conducted to assess and clarify the predictive risk factor of neurologic outcome in patients with acute carbon monoxide (CO) poisoning. METHODS: A total of 453 patients with acute CO poisoning were admitted to the emergency department of Samsung Changwon Hospital from January 2010 to June 2017. Patients with acute CO poisoning who were followed for >6 months were studied. Initial Glasgow Coma Score (GCS), serum neuron-specific enolase (NSE), and lactate were measured after emergency department arrival. Patients were divided into two groups (good vs poor neurologic outcome). RESULTS: A total of 432 patients (median age: 55 years, range: 17-91 years) were enrolled. There was a statistical difference between the good neurologic outcome group and the poor neurologic outcome group in terms of Exposure time, WBC, aspartate aminotransferase (AST), CK-MB, Troponin-I, creatinine kinase, NSE, lactate, CO-Hb, and GCS. NSE, lactate, and GCS were the early predictors of development of poor neurologic outcome. The areas under the curve in the ROC curve analysis for the GCS, NSE, and lactate were 0.842, 0.795, and 0.894, respectively. CONCLUSION: Initial serum lactate level may correlate with the patient neurologic outcomes and prove to be a useful prognostic factor. Also NSE, and GCS might be a useful additional parameters that could predict the neurologic outcome on acute CO poisoned patients.

Neuroprotective influence of sitagliptin against cisplatin-induced neurotoxicity, biochemical and behavioral alterations in Wistar rats.

Cisplatin has been extensively used as a chemotherapeutic agent since around 40 years, though its usage is limited due to severe adverse effects like neurotoxicity that might be because of oxidative stress. Hence, the present study was planned to investigate the possible protective role of sitagliptin against cisplatin-associated neurotoxic, biochemical, and behavioral alterations in male Wistar rats. Sitagliptin is a dipeptidyl peptidase-4 inhibitor that shows dual effects by improving the control on metabolism as well as decreasing the debility in cognitive function that is associated with increased insulin sensitivity and antioxidant property. For the in vitro assay, cultured rat pheochromocytoma (PC12) cells were exposed to different concentrations (10, 20, and 50 mM) of sitagliptin for 24 h. Cisplatin at 5 mM concentrations was added and cell viability was assessed using MTT assay. For in vivo study, animals were divided into four groups. Group I (Vehicle control): animals were administered 0.9% (w/v) of normal saline (1 mL/100 g; p.o.). Group II (Cisplatin): animals were treated with cisplatin (2 mg/kg; i.p.). Group III (Cisplatin + sitagliptin): animals were administered cisplatin along with sitagliptin. Group IV (Sitagliptin): animals were given sitagliptin (10 mg/kg; p.o.). All the treatments were administered for 8 weeks. On last day of treatment, behavioral evaluations including locomotor and rotarod studies were performed. In addition, several antioxidant enzymes were also estimated from cerebellum tissues; such as levels of thiobarbituric acid reactive substance (TBARS) were determined as a marker of lipid peroxidation, reduced glutathione (GSH) and catalase (CAT) were also estimated. Histological study of cerebellum tissue was also performed after performing the behavioral study. Exposure to cisplatin decreased cell viability in PC12 cells which were significantly increased by co-treatment with sitagliptin. In in vivo study, cisplatin significantly elevated the level of TBARS and reduced the level of antioxidant enzymes such as GSH and CAT which were significantly restored in sitagliptin + cisplatin group of rats. In addition, cisplatin impaired performance on the locomotor and rotarod activities, whereas sitagliptin significantly improved the performance of both activities. These results suggested the neuroprotective influence of sitagliptin by protecting cerebellum part of brain against cisplatin-induced toxicity.