Tag Archives: L-carnitine

Antioxidants as supplements during drug-induced thrombocytopenia: a comparative analysis of Vanillic acid, L-carnitine and Caripill™

M. Mithun, V. Rajashekaraiah*

Department of Biotechnology, School of Sciences,
JAIN (Deemed-to-be University), Bengaluru, Karnataka, India;
*e-mail: vani.rs@jainuniversity.ac.in

Received: 20 September 2023; Revised: 07 November 2023;
Accepted: 01 February 2024; Available on-line: 26 February 2024

Drug-induced thrombocytopenia (DIT) is a disorder where platelet count declines as an adverse effect of therapeutic drugs. Plant extract of C. papaya Caripill™ is known to elevate platelet count under thrombocytopenic conditions. To evaluate the contribution of supplements with antioxidant potential to treat DIT, the comparative study of Caripill™, vanillic acid L-carnitine effect on platelet count and indices of oxidative stress in a model of rat thrombocytopenia induced through oral administration of hydroxyurea was performed. Wistar rats were grouped into four categories with five animals in each group: control (without any treatment); control + antioxidants; thrombocytopenia; thrombocytopenia + antioxidants. The above-mentioned antioxidants were supplemented orally at 50 mg/kg for 7 days. The level of lipid peroxidation products­, superoxides, protein carbonyls and sulfhydryls, SOD and CAT activity in isolated platelets as oxidative stress markers, and indices of platelets aggregation and ATP secretion as functional markers were used. Vanillic acid was shown to be beneficial, similar to Caripill™, during hydroxyurea-induced thrombocytopenia by maintaining platelet functions, enhancing both the antioxidant capacity of platelets and its number. L-carnitine efficiently up-regulated the enzymatic antioxidants, maintained platelet functions and protected lipids and proteins from oxidation in thrombocytopenic rats, however, it could not improve the platelet count. These findings open new avenues for employing the studied antioxidants as supplements for therapeutic purposes.

Expression of antioxidant enzymes genes in the liver and cardiac tissues of rats under L-carnitine administration and high-intensity interval exercise training

B. Shahouzehi1,2, Y. Masoumi-Ardakani3, S. Aminizadeh3, H. Nasri2*

1Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran;
2Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
3Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran;
*e-mail: dr_hrnasri@yahoo.com
 
Received: 29 September 2020; Accepted: 07 July 2021

Reactive oxygen and nitrogen species are produced in the body both in normal and pathological processes and can alter cell redox and affect cell functions. Exercise training is able to modulate oxidant/antioxidants balance. In this study, we aimed to evaluate expression of antioxidant enzymes genes in the liver and cardiac tissues of rats that performed high-intensity interval training (HIIT) and received L-carnitine (LCAR). Thirty-two male Wistar rats were were randomly assigned into 4 groups (n = 8) as follows: 1. Untreated control; 2. The group that received LCAR (200 mg/kg/day i.p.); 3. The group that performed HIIT on a readmill (5 days/week for 4 weeks); 4. The group  that received LCAR and performed HIIT. At the end of the study, liver and cardiac tissues were excised and used to quantify glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT) and NF-κB genes expression by real-time PCR. It was found that both in LCAR and  HIIT groups GPX, SOD and NF-κB (P < 0.01) expression in cardiac and liver tissues was  significantly increased compared to the indices in the control group. In LCAR-HIIT group SOD and NF-κB expression in the liver was significantly increased compared to the group that received LCAR only (P = 0.046).  Our results showed that LCAR supplementation is useful to improve oxidative status in cardiac and liver tissues of rat during exercise training.

L-carnitine administration effects on AMPK, APPL1 and PPARγ genes expression in the liver and serum adiponectin levels and HOMA-IR in type 2 diabetes rat model induced by STZ and nicotinamide

B. Shahouzehi1,2, H. Fallah3, Y. Masoumi-Ardakani4*

1Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran;
2Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
3Department of Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;
4Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
*e-mail: ymab125@gmail.com

Received: 18 January 2020; Accepted: 25 June 2020

Diabetes is a chronic disease and a public health problem globally. L-Carnitine is synthesized in the liver, promotes fatty acids oxidation and currently is used as a supplement against weight gain. Carnitine level is found to be reduced in diabetic patients and to be beneficial as a supplement at diabetes, but the mechanisms­ of this effect is not fully understood. Therefore, we evaluated the oral L-carnitine supplementation on expression of AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma (PPARγ), adaptor protein APPL1 genes in the liver and insulin and adiponectin levels  in the serum of diabetic rats. Rats were randomly divided into three groups (n = 8) as follow: group 1 – control without any treatment, group 2 – diabetic control rats which received STZ (45 mg/kg) and nicotinamide (200 mg/kg) by i.p. injection, group 3 – diabetic rats which received 600 mg/kg/day carnitine orally for 35 days. It was found that L-carnitine supplementation reduced the level of fasting glucose compared to that in control and diabetic groups (P = 0.001,  P = 0.0001 respectively) and increased adiponectin level compared to diabetic nontreated rats (P = 0.0001). Homeostasis model assessment of insulin resistance (HOMA-IR) was significantly increased in the diabetic group and reduced in the group that received L-carnitine. These promising beneficial effect of L-carnitine on the type 2 diabetes in rats’ model was shown to be conducted through the up-regulation of AMPK, PPARγ and APPL1 genes expression in the liver and elevation of serum adiponectin level.

Carnitine effects on serum and pancreas inflammatory response in diabetic rats

Y. Masoumi-Ardakani1, H. Fallah2, B. Shahouzehi3

1Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
2Student Research Committee, School of Medicine,
Kerman University of Medical Sciences, Kerman, Iran;
3Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran;
e-mail: bshahouzehi@yahoo.com, bshahouzehi@gmail.com

Received: 08 May 2019; Accepted: 18 October 2019

Diabetes is a group of disorders characterized by elevated blood glucose and insulin secretion defect. Previous studies have reported L-carnitine beneficial and hypoglycemic effects in diabetic models. L carnitine anti-inflammatory properties in diabetes were not assessed perfectly, and there is a lack of information about this matter. Therefore, we designed this study and evaluated L-carnitine different doses supplementation on pro-inflammatory cytokines in STZ-induced diabetic rats’ pancreas and serum. We selected 48 male rats (200 ± 10 g) and randomly divided them into six groups (n = 8). Group 1, control; group 2, Diabetic control (DC); groups 3-6, STZ-induced diabetic rats which received L-carnitine different doses as follow; 300, 200, 100 and 50 mg/kg/day by intraperitoneal injection for 5 weeks. When the study ended, serum and pancreas samples were collected and cytokines levels were measured by specific ELISA kits. Our results showed that in diabetic rats, pro-inflammatory cytokines levels were elevated. Two L-carnitine doses 300 and 200 mg/kg/day showed beneficial effects and 300 mg/kg/day showed more effective and significant effects than other doses. The 300 mg/kg significantly reduced IL-1β and IL-6 levels in pancreas and serum. Our data proved the protective effects of intraperitoneal L-carnitine administration against diabetes and inflammation in diabetic rats. Indeed, L-carnitine long term supplementation through the intraperitoneal injection can be considered as a good and safe therapeutic strategy in diabetes.

Effect of L-carnitine administration on serum insulin and adiponectin levels, and AMPK, APPL1 and PPARγ gene expression in STZ-induced diabetic rat liver

B. Shahouzehi1, K. Barkhordari2, S. Aminizadeh3, Y. Masoumi-Ardakani4*

1Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Iran;
e-mail: bshahouzehi@yahoo.com;
2Department of Virology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran;
e-mail: khabatzanbil@gmail.com;
3Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Iran;
e-mail: soheilaminizadeh@gmail.com;
4Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Iran;
*e-mail: ymab125@yahoo.com

Diabetes is considered as a metabolic disease in which insulin secretion and functions are disturbed and characterized by hyperglycemia. L-carnitine is synthesized in most mammals and plays critical role in fatty acid oxidation and energy production. Data about the L-carnitine hypoglycemic effects are controversial. We evaluated long-term oral L-carnitine administration effects on blood glucose, insulin and adiponectin levels, as well as expression of AMPK, APPL1 and PPARγ genes in liver of STZ-induced diabetic rats. Group 1 (control), did not receive any treatment, group 2 received 50 mg/kg STZ by i.p injection, group 3 received single dose of 50 mg/kg STZ by i.p injection and also 600 mg/kg/day L-carnitine orally for 5 weeks. Our results showed that L-carnitine long-term oral supplementation significantly reduced blood glucose and normalized insulin levels in diabetic rats. Also, we found that L-carnitine significantly increased AMPK and APPL1 expression, and showed a mild elevation of PPARγ expression. In sum, we suggest that long-term L-carnitine supplementation has beneficial effects on diabetic rats which showed hypoglycemic effects. Probably the beneficial effects of L-carnitine are contributed to the upregulation of insulin sensitizers such as AMPK and adiponectin.