Thiamine Pyrophosphate Effect Research Articles

Protective effects of thiamine pyrophosphate and cinnamon against oxidative liver damage induced by an isoniazid and rifampicin combination in rats.

Abstract.Isoniazid and rifampicin (IRC) have been shown to cause hepa-totoxicity in both clinical and preclinical studies. Oxidative stress and in-flammation have been held responsible for the pathogenesis of IRC-induced hepatotoxicity. Antioxidative and anti-inflammatory effects of thiamine py-rophosphate (TPP) and cinnamon extract (CE) have been shown in previous studies. Therefore, our study investigated the protective effects of TPP and CE on possible liver damage caused by IRC treatment in rats. Twenty-four albino Wistar rats were categorized into four groups: a healthy group (HG), an IRC group (IRG), a TPP+IRC group (TIRG), and a CE+IRC group (CIRG). TPP (25 mg/kg) was administered intraperitoneally to TIRG, while CE (100 mg/kg) was administered orally to CIRG. In IRG, TIRG, and CIRG, isoniazid (50 mg/kg) and rifampicin (50 mg/kg) were administered orally one hour after these treatments. For seven days, this procedure was repeated once a day. After this period, blood samples were taken from the tail veins, and the rats were sac-rificed. The removed liver tissues were analyzed for oxidant, antioxidant, and proinflammatory cytokines and subjected to histopathological evaluation. Serum alanine aminotransferase and aspartate aminotransferase activities were also measured. An increase in malondialdehyde, nuclear factor kappa B, tumor necrosis factor-alpha, interleukin 1 beta, and interleukin-6 levels, a decrease in total glutathione levels, superoxide dismutase and catalase activi-ties, and an increase in alanine aminotransferase and aspartate aminotrans-ferase activities were found with IRC treatment (p<0.001). The histopatho-logical analysis of the IRG suggested hepatotoxicity (p<0.001). TPP and CE administered with IRC inhibited the biochemical changes (p<0.001). In the TIRG, this inhibition was higher than in the CIRG (p<0.05). Histological damage was inhibited by TPP (p<0.001). CE prevented biochemical changes but not histological changes except inflammatory cell infiltration. Therefore, TPP may be better than CE in preventing IRC-induced hepatotoxicity.

Effect of thiamine pyrophosphate on oxidative damage in the brain and heart of rats with experimentally induced occlusion of the common carotid artery.

Effect of thiamine pyrophosphate on oxidative damage in the brain and heart of rats with experimentally induced occlusion of the common carotid artery.

Pulmonary toxicity associated with high-dose favipiravir and treatment options: biochemical and histopathological evaluation.

Favipiravir is a broad-spectrum antiviral drug that is a viral RNA-dependent RNA polymerase inhibitor. Favipiravir is used in high doses to treat COVID-19 but has a side effect on humans at high doses. The side effects of favipiravir have been associated with oxidative stress in the literature. In this trial, we investigated the biochemical and histopathological effects of lacidip-ine, thiamine pyrophosphate (TTP), and adenosine triphosphate (ATP), drugs with antioxidant properties, on the lung toxicity caused by high-dose favipiravir in rats. The rats were classified into five groups: healthy (HG), favipiravir alone (Fav), lacidipine+favipiravir (LFav), TPP+favipiravir (TFav), and ATP+favipiravir (AFav). Favipiravir (800 mg/kg) was administered twice daily for seven days. Laci-dipine (4 mg/kg), TPP (20 mg/kg), and ATP (25 mg/kg) were administered once daily for seven days. Oxidant (malondialdehyde), non-enzymatic (total glutathi-one), and enzymatic (superoxide dismutase and catalase) antioxidant levels were measured in the excised lung tissues. Furthermore, the tissues were histopatho-logically examined. The systemic administration of high doses of favipiravir in-creased oxidant levels and decreased antioxidant levels in the lung tissue of rats. In parallel, the histopathological examination of the lung tissue revealed the presence of severe mononuclear cell infiltrations in interstitial areas and pronounced lymphoid hyperplasia. Lacidipine exhibited superior efficacy in mit-igating oxidative stress and preventing the decline of antioxidants induced by favipiravir compared with TPP and ATP. Histopathologically, the lacidipine admin-istration significantly reduced lung oxidative damage. TTP moderately reduced severe favipiravir-associated lung injury. However, ATP was ineffective against fa-vipiravir-associated lung injury. Lacidipine offers more therapeutic benefits than TPP in treating oxidative lung injury caused by high doses of favipiravir.

Effect of Thiamine Pyrophosphate on Amiodarone-Induced Oxidative Kidney Damage in Rats

Effect of Thiamine Pyrophosphate on Amiodarone-Induced Oxidative Kidney Damage in Rats

Effect of Thiamine Pyrophosphate Upon Oxidative Brain Injury Induced by Ischemia-Reperfusion in Rats

Effect of Thiamine Pyrophosphate Upon Oxidative Brain Injury Induced by Ischemia-Reperfusion in Rats

Effect of thiamine pyrophosphate on the characteristics of farrowing and piglet vitality

Asphyxia is considered the main non-infectious cause of prepartum mortality in swine, as well as an important factor that negatively affects neonatal vitality and can trigger physiological and metabolic disorders. Hence, the search for pharmacological protocols to reduce the harmful effects of asphyxia is a key area of research. Recent observations show that administering thiamine pyrophosphate (TPP) prior to a hypoxic event in certain species (rabbits, rats) has a neuroprotector effect that preserves energy metabolism under hypoxic conditions. Given this, the objective of this study was to evaluate a prophylactic protocol in high- and low-vitality neonate piglets based on TPP's effect on physiological and metabolic responses, body temperature, and weight. A total of 149 piglets born from 15 multiparous sows were used. The dams were randomly divided into two groups: control (NaCl 0.9%) and TPP (25 ml of TTP) administered 24 and 12 h before the expected farrowing date. The following reproductive variables of the sows were recorded: duration of farrowing, total number of piglets born per litter, number of liveborn piglets per litter, number of stillbirths and mummified fetuses at birth, and number of live piglets at weaning. In addition, the expulsion interval and vitality of all neonates were evaluated, body temperatures were recorded at ten intervals, and physiological profiles (blood gases, electrolytes, glucose) were registered for each neonate. Results show that the TPP-treated sows had shorter farrowing duration (P = 0.0060) and higher percentage of high-vitality neonates (60%). Moreover, their offspring exhibited greater vitality, fewer imbalances in their physiological and metabolic profiles, and greater weight gain at weaning (P < 0.0001). Findings suggest that administering TPP exerts a protective effect when hypoxic events occur, though this differs from results obtained with rat pups, where applying TPP after such events did not provide protection from asphyxia-induced damage. These differences may be due to the moment at which TPP was applied. The application time we selected was distinct from the procedure followed with rats because it was based on a dataset that describes the influence of administering TPP as a prophylactic treatment before a hypoxic event. Prophylactic administration of TPP to sows at the end of gestation exerted a neuroprotective effect on neonatal vitality and gas exchanges and energy metabolism in the offspring that were reflected in the greater weekly weight gain in those piglets.

Effect of Thiamine Pyrophosphate upon Possible Metamizole-Induced Liver Injury in Rats

Effect of Thiamine Pyrophosphate upon Possible Metamizole-Induced Liver Injury in Rats

The Testicular Protection Effect of Thiamine Pyrophosphate Against Cisplatin-treated Male Rats

Infertility is a worldwide problem affecting both genders, it can be defined as the inability of the adult males to make a fertile woman pregnant after one year of regular intercourse. Cisplatin considers one of the most potent antineoplastic drugs that is extensively&#x0D; &#x0D; used, alone or in combination with other antitumor agents, to manage solid and germ cell cancer. The major drawback in cisplatin treatment is its damaging consequence on various body tissue, including the testis, liver, renal and others. One of its pronounced adverse effects is testicular injury, which may proceed to end with infertility. Thiamine pyrophosphate is the active form of thiamine which has an important role in the oxidative phosphorylation pathway. It acts as a co-factor and energy source for many cellular enzymes, also it utilizes by pentose-phosphate shut that elevates NADPH and improves antioxidants level. This study aimed to evaluate the effect of thiamine pyrophosphate on sperm parameters and gonadotropic hormones (luteal and follicle-stimulating hormone) of male rats exposed to a single dose of cisplatin.&#x0D; Twenty-eight albino male rats were randomly grouped into four groups. Control group: received normal saline, Cisplatin group: received normal saline and cisplatin, TPP50 group: received thiamine pyrophosphate (50mg/kg) with cisplatin, and TPP100 group: as third group (TPP50) but thiamine pyrophosphate dose was 100 mg/kg. Semen samples used to measure the sperms viability and morphology, while serum samples were gathered to measure the levels of gonadotropic hormones (FSH and LH).&#x0D; This study revealed that rat’s testicular function was notably deteriorated by cisplatin administration, represented by a reduction in sperm parameters (viability and normal morphology), and serum gonadotropic hormones (FSH and LH). In this work, thiamine pyrophosphate was act as a protective agent that ameliorates rat’s testicular damage induced by cisplatin in a dose-dependent manner. The suggested mechanism may attribute to its antioxidant and anti-apoptotic action

Effect of thiamine pyrophosphate on cyclophosphamide-induced oxidative ovarian damage and reproductive dysfunction in female rats.

Cyclophosphamide is a drug used in various types of cancer. It can cause oxidative and inflammatory ovarian damage and infertility. Thiamine pyrophosphate (TPP) to be investigated for its effect on cyclophosphamide-induced ovarian damage and reproductive dysfunction in the present study is the active metabolite of thiamine. It has been shown that TPP protects organs and tissues from oxidative stress and proinflammatory cytokine damage. To investigate the effect of TPP against the ovarian damage and reproductive dysfunction caused by cyclophosphamide in rats. Albino Wistar type female rats were divided into healthy control (HG), cyclophosphamide (CYC) and TPP + cyclophosphamide (TPPC) groups (for each group, n = 12). Thiamine pyrophosphate at a dose of 25 mg/kg was injected intraperitoneally (ip.) in the TPPC group, and 0.9% NaCI solution was injected ip. in the CYC and HG groups. One hour after the injection, 75 mg/kg of cyclophosphamide was administered ip. in the TPPC and CYC groups. This procedure was repeated once a day for 30 days. At the end of this period, 6 rats from each group were euthanized with a high dose of anesthetic (50 mg/kg of sodium thiopental). Biochemical and histopathological examinations were performed on the extracted ovarian tissue. The remaining animals were kept in the laboratory with mature male rats for 2 months for reproduction. Thiamine pyrophosphate significantly decreased the cyclophosphamide-induced increase in the levels of the oxidant parameter malondialdehyde (MDA), proinflammatory nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β). In addition, TPP decreased the severe histopathological damage associated with cyclophosphamide in the ovarian tissue and prevented infertility. Our experimental results have suggested that TPP could be beneficial in the treatment of cyclophosphamide-induced ovarian injury and infertility.

The effects of thiamine pyrophosphate on propofol-induced oxidative liver injury and effect on dysfunction.

Propofol may cause an increase in reactive oxygen species in the body. In this study, we tested the effect of antioxidant thiamine pyrophosphate (TPP) on propofol-induced liver damage. The eighteen rats were split into three groups: HG, healthy; PP, propofol-treated (50 mg/kg) and PT, treated with propofol (50 mg/kg) and TPP (25 mg/kg). Total glutathione (tGSH), total oxidant (TOS), and total antioxidant (TAS) levels were tested together with aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and malondialdehyde (MDA). Histopathological examination of the tissues was performed. We have found that levels of MDA, TOS, ALT, AST, and LDH were all higher in PP group than in HG and PT groups (p < 0.05). In PP group, the TAS and tGSH levels were statistically substantially lower. The PT for oxidants levels showed a statistically significant reduction. In PT group, the levels of antioxidants were found to be considerably higher. The epitheliums, glands, and vascular structures of the PTs were histologically close to normal. By boosting antioxidants, TPP may help to reduce propofolinduced liver damage.

Prevalence of Thiamine Deficiency in Chronic Heart Failure Patients: Ramathibodi Cardiology Clinic Experience

Objective: Thiamine deficiency is still a public health concern in developing countries including Thailand. Heart failure is associated with thiamine deficiency especially in patients receiving diuretic therapy. Therefore, we sought to find the prevalence of thiamine deficiency in chronic heart failure outpatients. Materials and Methods: A cross-sectional descriptive epidemiological study in 50 heart failure patients scheduled for regular follow-up visits at Ramathibodi Cardiology Clinic, Mahidol University, Bangkok, Thailand. Thiamine pyrophosphate effect was used to identify thiamine deficiency. Review of electrical medical records were made in order to collect variable clinical and demographic data. Results: The mean age was 60&plusmn;2.1 years, 54% were male. The mean left ventricular ejection fraction was 37&plusmn;2.5%. The prevalence of thiamine deficiency in a chronic heart failure outpatient was 6% (n=3). Thiamine status was negatively associated with left ventricular ejection fraction (r=-0.283, p=0.047) and thiamine status was positively associated with left ventricular dimension (r=0.462, p=0.001). However, there was no association between the dose of diuretic and thiamine status (r=0.024, p=0.882), duration of heart failure and thiamine status (r=-0.012, p=0.945). In patients with severe thiamine deficiency, there were subsequent serious adverse cardiovascular outcomes (one had cardiac arrest and underwent left ventricular assist device). Conclusion: We found that the prevalence of thiamine deficiency in chronic heart failure outpatients is low in an urban outpatient setting. Keywords: Thiamine deficiency; Heart failure; Prevalence

Thiamine pyrophosphate improved vascular complications of diabetes in rats with type 2 diabetes by reducing glycation, oxidative stress, and inflammation markers.

Background: Thiamine deficiency contributes to hyperglycemia and diabetes complications. Thus, in this study, the effect of thiamine pyrophosphate (TPP) on the in vivo and in vitro formation of glycation, oxidative stress, and inflammatory markers (the main contributors of vascular diabetes complications) was examined in type 2 diabetes rat model. Methods: Type 2 diabetes was induced in rats with a combination of streptozotocin and nicotinamide (55+200 mg/kg). Two groups of rats, healthy and diabetic, were treated with 0.1% TPP in drinking water daily for 3 months and the 2 others received water only. The glucose, insulin, early to end glycation products, the activity of glyoxalase system, lipid profile, LDL oxidation markers, inflammatory markers, creatinine in the serum, and proteinuria in the urine of all rats were determined. Moreover, albumin and LDL were incubated with glucose in the presence and absence of TPP, and the samples were investigated for glycation and oxidation products. Different variables in all 4 groups were compared with multiple analysis of variance (MANOVA-Tukey) test using SPSS version 16. Significance level was set at p<0.05. Results: TPP decreased the formation of diverse glycation and oxidation products in both in vivo (glycated LDL= 144.50±3.48 and oxidized LDL= 54.08±2.67 μmol/l) and in vitro (glycated LDL= 107.00±2.82 and oxidized LDL= 50.83±1.22 μmol/l). In addition, the vitamin reduced fasting blood sugar (9.23±0.29), insulin resistance (9.10±0.50), tumor necrosis factor-α (285.43±15.97), interleukin-6 (257.65±13.06), and improved the lipid profile, the activity of Glo system (Glo-I= 31.65±1.06 and Glo-II= 27.01±0.90 U/mL) and renal function in the diabetic rat (p<0.001). Conclusion: TPP decreased the major risk factors for diabetic complications and corrected the alternations of glucose and lipid metabolism in type 2 diabetic rats; thus, it is recommended for diabetes treatment.

Biochemical Investigation of the Protective Effect of Thiamine Pyrophosphate on Methotrexate-Induced Gastrotoxicity in Rats

Biochemical Investigation of the Protective Effect of Thiamine Pyrophosphate on Methotrexate-Induced Gastrotoxicity in Rats

The effects of thiamine pyrophosphate on ethanol induced optic nerve damage

BackgroundWe aimed to determine the protective effects of thiamine pyrophosphate on ethanol induced optic neuropathy in an experimental model.MethodsThe rats were assigned into 4 groups, with 6 rats in each group as follows: healthy controls (HC group), only ethanol administered group (EtOH group), ethanol + thiamine pyrophosphate (20 mg/kg) administered group (TEt-20 group), and only thiamine pyrophosphate (20 mg/kg) (TPG group) administered group. To the rats in TEt-20 and TPG groups, 20 mg/kg thiamine pyrophosphate was administered via intraperitoneal route. To the rats in HC and EtOH groups, the same volume (0.5 ml) of distilled water as solvent was applied in the same manner. To the rats in TEt-20 and EtOH groups, one hour after application of thiamine pyrophosphate or distilled water, 32% ethanol with a dose of 5 g/kg was administered via oral gavage. This procedure was repeated once a day for 6 weeks. From the blood samples and tissues obtained from the rats, Malondialdehyde (MDA), reduced glutathione (GSH), interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were studied. Histopathological evaluations were performed to the optic nerve tissue.ResultsSerum and tissue IL-1β, TNF-α and MDA levels were the highest in EtOH group which were significantly lower in thiamine pyrophosphate administered group (TEt-20 group) (p: 0.001). Serum and tissue reduced GSH levels were the lowest in EtOH group which were also significantly higher in TEt-20 group (p:0.001). In histopathological evaluations, in EtOH group there was obvious destruction and edema with hemorrhage and dilated blood vessels which were not present in any other groups.ConclusionsThere was an apparent destruction in ethanol administered group in histopathological analyses with an augmented level of oxidative stress markers and all those alterations were prevented with concomitant thiamine pyrophosphate administration. These protective effects of thiamine pyrophosphate are extremely important in chronic ethanol consumption. Clinical studies are warranted to define the exact role of thiamine pyrophosphate in prevention of ethanol induced optic neuropathy.

Role of thiamine supplementation in the treatment of patients with heart failure: A double-blind randomized controlled trial

Introduction: The role of thiamine supplementation in heart failure (HF) patients has shown conflicting results and has not been adequately studied. Aims and Objectives: The aim and objective were to determine whether thiamine supplementation will provide clinical, biochemical, and echocardiographic benefit in congestive HF patients. Materials and Methods: In this single-center, double-blind, prospective randomized controlled trial, HF patients with varied etiology were included. Patients were randomly allocated to 1 week of inpatient double-blind intravenous therapy with either placebo or thiamine. Parameters studied included clinical, Echo left ventricular ejection fraction (LVEF), and thiamine pyrophosphate effect (TPPE) levels before/after treatment. After completion of 1-week treatment, all patients were given oral thiamine and evaluated at the outpatient clinic after 6 weeks. Results: A total of fifty patients were studied. There was no difference at baseline in mean age (61.4 ± 7.1 vs. 62.4 ± 8.0 years), sex (males 52% vs. 56%), etiology (idiopathic dilated cardiomyopathy 68% vs. 60%, ischemic heart disease 20% vs. 24%), clinical parameters, TPPE levels (16.4 ± 5.2 vs. 16.2 ± 6.5%), and LVEF (28.1% ± 6.7% vs. 28.3% ± 6.6%) in thiamine as compared to placebo group. After 1 week of treatment, there was significant improvement in systolic blood pressure (119.2 ± 18.3 vs. 106.1 ± 18.9 mmHgP Conclusions: Thiamine supplementation significantly improved clinical and echocardiographic parameters. Thiamine supplementation is cost-effective, is benign, and is easily available with significant clinical benefits.

Prevalence of and factors associated with thiamin deficiency in obese Thai children.

Obesity is a state that results from excessive energy consumption, and obese people often have micronutrient deficiencies. The objective of this study was to investigate the prevalence of and factors associated with thiamin deficiency in obese Thai children. This cross-sectional study was conducted at Faculty of Medicine Siriraj Hospital, Mahidol University during 2014 to 2017. Children aged 7-15 years old with exogenous obesity were recruited. Symptoms and signs of thiamin deficiency were evaluated. Erythrocyte transketolase activity was measured by thiamin pyrophosphate effect (TPPE), with ≥15% indicating thiamin deficiency. Dietary consumption from a 5-day food diary and food frequency questionnaire was calculated by INMUCAL software. Other medical complications of obesity were also evaluated. One hundred and twenty-four subjects (81 males and 43 females) were enrolled, with a mean age of 10.9 years. Fifty-two subjects had abnormal TPPE for an overall prevalence of thiamin deficiency of 42%. Manifestations of thiamin deficiency included numbness, weakness, and calf muscle cramping. TPPE test results were correlated with at least one symptom or a sign of thiamin deficiency (p<0.01). The thiamin-deficient group tended to have higher proportion of morbid obesity and larger waist circumferences than thiamin-sufficient group. The thiamindeficient group tended to consume less thiamin in relation to energy intake than the thiamin-sufficient group (p=0.057). Items of foods consumed were statistically indistinguishable between groups. The results of this study revealed a 42% prevalence of thiamin deficiency among obese Thai children, and most of those cases were subclinical.

Thiamine status, metabolism and application in dairy cows: a review.

As the co-enzyme of pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, thiamine plays a critical role in carbohydrate metabolism in dairy cows. Apart from feedstuff, microbial thiamine synthesis in the rumen is the main source for dairy cows. However, the amount of ruminal thiamine synthesis, which is influenced by dietary N levels and forage to concentrate ratio, varies greatly. Notably, when dairy cows are overfed high-grain diets, subacute ruminal acidosis (SARA) occurs and results in thiamine deficiency. Thiamine deficiency is characterised by decreased ruminal and blood thiamine concentrations and an increased blood thiamine pyrophosphate effect to >45 %. Thiamine deficiency caused by SARA is mainly related to the increased thiamine requirement during high grain feeding, decreased bacterial thiamine synthesis in the rumen, increased thiamine degradation by thiaminase, and decreased thiamine absorption by transporters. Interestingly, thiamine deficiency can be reversed by exogenous thiamine supplementation in the diet. Besides, thiamine supplementation has beneficial effects in dairy cows, such as increased milk and component production and attenuated SARA by improving rumen fermentation, balancing bacterial community and alleviating inflammatory response in the ruminal epithelium. However, there is no conclusive dietary thiamine recommendation for dairy cows, and the impacts of thiamine supplementation on protozoa, solid-attached bacteria, rumen wall-adherent bacteria and nutrient metabolism in dairy cows are still unclear. This knowledge is critical to understand thiamine status and function in dairy cows. Overall, the present review described the current state of knowledge on thiamine nutrition in dairy cows and the major problems that must be addressed in future research.

The Protective Effect of Thiamine Pryophosphate Against Sugar-Induced Retinal Neovascularisation in Rats.

The aim of this study was to investigate the effect of thiamine pyrophosphate (TPP), administered via sugar water, on retinal neovascularisation in rats. Animals were assigned to three groups, namely the TPP sugar-water group (TPSWG, n = 12), the control group (CG, n = 12) and the healthy group (HG, n = 12). The TPSWG was injected intraperitoneally with TPP once a day for 6 months. CG and HG rats were given distilled water in the same way. TPSWG and CG rats were left free to access an additional 0.292 mmol /ml of sugar water for 6 months. The fasting blood glucose (FBG) levels of the animals were measured monthly. After 6 months, biochemical, gene expression and histopathologic analyses were carried out in the retinal tissues removed from the animals after they were killed. The measured FBG levels were 6.96 ± 0.09 mmol/ml (p < 0.0001 vs. HG), 6.95 ± 0.06 mmol/ml (p < 0.0001 vs. HG) and 3.94 ± 0.10 mmol/ml in the CG, TPSWG and HG groups, respectively. The malondialdehyde (MDA) levels were found to be 2.82 ± 0.23 (p < 0.0001 vs. HG), 1.40 ± 0.32 (p < 0.0001 vs. HG) and 1.66 ± 0.17 in the CG, TPSWG and HG, respectively. Interleukin 1 beta (IL-1β) gene expression was increased (3.78 ± 0.29, p < 0.0001) and total glutathione (tGSH) was decreased (1.32 ± 0.25, p < 0.0001) in the retinal tissue of CG compared with TPSWG (1.92 ± 0.29 and 3.18 ± 0.46, respectively). Increased vascularisation and oedema were observed in the retinal tissue of CG, while the retinal tissues of TPSWG and HG rats had a normal histopathological appearance. A carbohydrate-rich diet may lead to pathological changes in the retina even in nondiabetics, but this may be overcome by TPP administration.

The effect of thiamine and its metabolites on peripheral neuropathic pain induced by cisplatin in rats.

Thiamine pyrophosphate (TPP) is the active metabolite of thiamine. This study aimed to investigate the effects of thiamine and TPP on cisplatin-induced peripheral neuropathic pain (PNP). Male albino Wistar type Rattus norvegicus were divided into six groups (n=6) that received 2 mg/kg cisplatin (CIS), 25 mg/kg thiamine (TM), 2 mg/kg cisplatin+25 mg/kg thiamine (CTM), 25 mg/kg TPP (TPP), 2 mg/kg cisplatin+25 mg/kg TPP (CTPP), or distilled water (healthy group; HG) for 8 days intraperitoneally. Analgesic effect was measured with a Basile Algesimeter. IL-1β, malondialdehyde (MDA), total glutathione (tGSH), thiamine, and TPP were determined in blood samples. Histopathological examinations were performed on removed sciatic nerves. The percent analgesic effects of the CTM and CTPP groups were calculated to be 21.3% and 82.9%, respectively. Increased production of IL-1β and MDA by cisplatin was inhibited by TPP, while it was not inhibited by thiamine. Conversion of thiamine to TPP significantly decreased in the CIS group. Histopathological and biochemical investigations demonstrated that hyperalgesia and sciatic nerve damage developed in the CIS and CTM groups with low TPP levels. These results indicate that cisplatin inhibits the formation of TPP from thiamine, leading to severe PNP. This finding suggests that TPP may be more beneficial than thiamine for the treatment of cisplatin-induced PNP.

Gene expression and histopathological evaluation of thiamine pyrophosphate on optic neuropathy induced with ethambutol in rats.

To compare the effects of thiamine pyrophosphate (TPP) and thiamine (TM) in oxidative optic neuropathy in rats induced by ethambutol. The animals were divided into four groups: a control group (CG), an ethambutol control (ETC) group, TM plus ethambutol group (TMG), and TPP plus ethambutol group (TPPG). One hour after intraperitoneal administration of TM 20 mg/kg to the TMG group and TPP 20 mg/kg to TPPG group, 30 mg/kg ethambutol was given via gavage to all the groups but the CG. This procedure was repeated once daily for 90d. After that period, all rats were exposed to high levels of anaesthesia in order to investigate the gene expression of malondialdehyde and glutathione in removed optic nerve tissue and histopathologically to examine these tissues. Malondialdehyde gene expression significantly increased, whereas glutathione gene expression significantly decreased in the ETC group compared to the CG. TM could not prevent the increase of malondialdehyde gene expression and the decrease of glutathione, while TPP significantly could suppress. Histopathologically, significant vacuolization in the optic nerve, single-cell necrosis in the glial cells, and a decrease in oligodendrocytes were observed in the ETC group. Vacuolization in the optic nerve, a decrease in oligodendrocytes and single-cell necrosis were found in the TMG group, while no pathological finding was observed in the TPPG group except for mild vacuolization. TPP protects the optic nerve against the ethambutol-induced toxicity but TM does not. TPP can be beneficial in prophilaxis of optic neuropathy in ethambutol therapy.