<<

©2016 ASP Ins., Afarand Scholarly Publishing Institute, Iran ISSN: 2252-0805 Quarterly of the Horizon of Medical Sciences 2016;22(3):229-235 Comparison the Protective Effects of L- and Acetyl L-Carnitine on Blood and Peroxidation Level in Diabetic Rats

A R T I C L E I N F O A B S T R A C T Aims Article Type New medications with less side-effect are increasingly noticed now a day. L-Carnitine and Acetyl L-Carnitine reduce the secondary side-effects of Type I . The aim of this Original Research Authors Materialsstudy was & to Methods investigate the effects of oral administration of the materials on the blood PhD, glucose and the lipid per-oxidation of the liver and brain tissues in the diabetic rats. 1 DVM, In the experimental study, 50 male Wistar rats were studied. The rats 1 Hajinezhad M.R.*DVM, were randomly divided into five groups including control (the healthy rats), negative control Hajian Sh. 2 PhD, Saghayei S.3 PhD (the diabetic rats), and three treatment diabetic groups. The diabetic groups received 110mg/ Samzadeh-Kermani A.R. Kg alloxan via injection to become diabetic. The treatment groups received L-Carnitine, Acetyl Nabavi R. L-Carnetine, and L-Carnetine with Acetyl L-Carnetine (300mg/Kg) as gavage for 30 days. The How to cite this article lipid per-oxidation, the serum glucose, the lipid profile, and the liver were measured Findingsat the end of the experiment. Data was analyzed using one-way ANOVA followed by Tukey Hajinezhad M.R, Hajian Sh, complementary test. Saghayei S, Samzadeh-Kermani The blood concentration, , cholesterol, creatinine, the serum A.R, Nabavi R. Comparison the liver enzymes, and the level of the liver tissue malondialdehyde significantly decreased Protective Effects of L-Carnitine in treatment diabetic group than diabetic group without any treatment, while HDL level and Acetyl L-Carnitine on Blood Glucose and Lipid Peroxidation increased as well (p<0.05). The brain tissue malondialdehyde and the serum HDL decreased Level in Diabetic Rats. Quarterly and increased due to the administration of Acetyl L-Carnitine, respectively. Nevertheless, it of the Horizon of Medical Sciences. Conclusionaffected no other parameter significantly. The positive effects of L-Carnitine were reduced by 2016;22(3):229-235. the administration of Acetyl L-Carnitin with L-Carnitine. The administration of L-Carnitine further reduces the secondary side-effects of diabetes than Acetyl L-Carnitine. In addition, simultaneous administration of the materials isKeywords not recommended.

Diabetes Mellitus; L-Carnitine; Acetyl L-Carnitine; Rats C I T A T I O N L I N K S [1] [2] [3] Preserved β-cell[4] function in type 1 diabetes by ... Modulation of tissue fatty acids by L-carnitine[5] attenuates ... The effect of two-week l-carnitine[6] supplementation on *Basic Science Department, Veteri- exercise-induced ... L-Carnitine treatment for congestive : Experimental 1 [7] nary Medicine Faculty, University and ... L-carnitine supplementation for the treatment of ... A review on the role of Zabol, Zabol, Iran [8] Basic Science Department, Veteri- of in the management of ... Toward a biomarker[9] of oxidative stress: A nary2 Medicine Faculty, University fluorescent probe for exogenous and ... Comparison of E, L-carnitine and of Zabol, Zabol, Iran in ameliorating carbon tetrachloride and ... In vivo effect of acetyl-L- Chemistry Department, Basic Sci- [10] ence3 Faculty, University of Zabol, carnitine on succinate oxidation, adenine nucleotide pool and lipid composition[11] of synaptic Zabol, Iran and non-synaptic mitochondria from ... Protective effect of hydro[12] alcoholic extract Pathobiology Department, Veteri- from Prosopisfarcta leaves on lipid peroxidation of serum and ... Preventive effect nary Faculty, University of Zabol, [13] Zabol, Iran of berberisintegerrima on the serum levels of glucose and [14] in ... Assay for lipid Correspondence peroxides in animal tissues by ... Effect of hydroalcoholic extract of Prosopisfarcta Address [15] pod on liver histopathology and malondialdehyde level in ... L-carnitine[16] is essential : Basic Science Department, to beta-oxidation of quarried from ... Therapeutic effect of L-carnitine on Veterinary Medicine Faculty, Univer- sialic acid, soluble Fas (sFas) and other biochemical variables in ... Comparison of the sity of Zabol, Bonjar Ave, Zabol, Iran. [17] Phone +985422323567 effects of L-carnitine and acetyl-L-carnitine on carnitine levels, ambulatory activity, and FaxPostal Code: 98613-35856 [18] [19] : ... Levels of carnitines in[20] brain and other tissues of rats of different ages: effect of ... : +985422323567 [21] Effects of short-term l-arginine supplementation on lipid profile and ... [22] Protective [email protected] effect of L-carnitine and ... L-Carnitine changes the levels of insulin-like growth ... Article History [23] Effects of L‐carnitine[24] treatment on oxidant/[25] state and ... Acetyl-L- Carnitine and nicotinamide for[26] prevention of ... L-carnitine inhibits hypoglycemia- Received: October 24, 2015 induced brain ... Acetyl-L-carnitine enhances ... Acetyl-L-carnitine and lipoic Accepted: May 10, 2016 acid improve mitochondrial ... Protective effects of L-carnitine on myoglobinuric acute ... Copyright©ePublished: June2016 30, ASP 2016 Ins. This open-access article is published under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License which permits Share (copy and redistribute the material in any medium or format) and Adapt (remix, transform, and build upon the material) under the Attribution-NonCommercial terms. // :'0+ 1+% // :-2 1+% * [email protected] :&34 54 * . PhD !" #$ %& ! ' () * DVM /& 0 12$ 3(!- 4!5 +,- [1] :' 89 $ ' #7 6- . - DVM 6- !$ .- ;!)7 !$ !$ . -! : <9 ,-= >- !5 PhD ! ?'- 6 !5 !- ( ,-= ! )$ #" ,$!- @5 A0 B! PhD "# . "#$!% F2& (D" E 6- .- C=

.[2] #" $<7 3($ E )$!= H 6,> ) 63+ 2D(G- !$ 37 + . 75$ )*+ , : . ?" 649 $ ! ,"" ! ,""! -" 7,""! "$$ 7"$ 2=$ .[4]" #$ Y>0 - 1- W XE9 (> (&" 6&" /4") ,""! -" Y!)5 :- :$ !$ @! ,""! "$ 2=$ : C- #B ?$ .- !5 !- ( ,-= 7/3 4& 2& 6D) A 7/ / 6 $ [ @- Q ,9 [ - 3(!- ,"D 7 4 ,"D"$ 7!& 7"&$ )$ %! ) 6- $5 + . D 2: 4: HDL /4" 2: "* /* /4" 9O\ H ,M . #$ (= + - 2: "* /* ,""! -" 45$ .(p</) 6 !@,!,& 6B -9 W,> - 6- .2 D) # < 7 HDL 4: 49 !$ @! )$!= :T9 ]JU H . ,""! 2 (# 7,""! ,""! -" 45$ #" )$ #$ . 6 2:H <:E . ) S ^B!)- ^B!)- 2O )$ != ,""! -" ,""! 45$ : #$ ^B!)- 2O )$!= - . 6 2D(G- 45$ ,"D . 0" "#$ 2 " # )$!= - D ^L, U = . ">$ , /4 ?= 1 )$!= " ^!) . #B )$ ./ - *!(!+,& !() *!(!+,& ' :&$%

,9 1 !(X 37X<- !> C= 5 ! " ^!) $$ #$ .- #$ = @9 2O !"7 L ! ;- _ 1= ( #" )$!= ? &3 6> Y>-= . 76 ( h-=%&) $ _ 6+,& ;& Q!4& d,' Y dJE .,!"7 E AST (J),-=V=) ALT k^= Y & dJE bTN- @K- $ <" V= 6Y! 6J! (J),-=2R=) 2U .- eD Q dJE . - $ @D(! % (,< hSelectra pro M) ( h5 ' $) ;- bTN- [ A= .,!"7 E #+, - ( h-=%&) = : ^)B 67 W,& "T Z ;- .,! ! :(MDA) "# ! J,-!,$ 67 ( 1(^( KO ;-) !,$ 67 ( 1(l45 9 U !>$) >$= d& #-= & K X! 67 ( 1()$(= 6! KO ;- ) 1 ( >!) d& ' c- :$ K ! 67 ( 1!$ 37<$ 37X<- 6F d " 6 . 76 67 ( !$ @! 37<$ 37X<- ?N 7<' . FJ! 66F 5 C . 65 ;- 2-

Q Horizon Med Sci Vol. 22, Iss. 3, Sum 2016 Z HDL - - 1 5 !)<$ )<7 1%Q! C, !$ Z c- " `(= (- - 1!$ @! + ! 67 & 5 3 ! $<7 L< 1(p</) #$ ! 67 :) ,D- 67 :) k,D- Z !$ K H !$ . ,D- H :$ " `(= (- - .(p</) " #$ (- X! 67) J,-!,$ - - 1 c- " R( )$& ,D- )<7 - 1!$ K ! 67 !$ - + . #$ :$ " `(= (- !$ - ! 67 ,D- Z 3 !)<$ - < 1> 6- H B ?: C, !$ @! 67 :) HDL - ) !$ .(p</) 3$ + :) !$ - !" `(= (- .(p</) #" ,D- Z J,-!,$ .( ') #$ C, - - ,D- H !$ @! ! 2

> "6 + ./ "6- ;, < '0 !=$>" $ ! ) !!! "6(+ ( , '78 49 ( '% () = 6 + @%) % +' ++( %- ++( %- ++( %- %( +( %- '+, %- ( " )&*+ +' + +' + +' ((!$) !) -"- /±/ /±/ /±/ /±/ /±/ / + + /±/ /±/ /±/ /±/ /±/ + + "( &+ /±/ /±/ /±/ /±/ /±/ ((!$) !) &(4, /±/ /±/ /±/ /±/ /±/ ((!$) !) 4!% /±/ /±/ /±/ /±/ /±/ ((!$) !) HDL-C /±/ /±/ /±/ /±/ /±/ ((!$ ) AST /±/ /±/ /±/ /±/ /±/ ((!$ ) ALT /±/ /±/ /±/ /±/ /±/ ((!$) !) *!5!%, ('0 ! &) " /±/ /±/ /±/ /±/ /±/ < '0 + /±/ /±/ /±/ /±/ /±/ ;, '0 +

$<7 6@C) >! #" 6- . ATP C- #B (<7 )- ^= 5 $D" < ,E #$ ,D- H !$ > W! + 1\U .[13, 14] 5 ,E #$ !$

= @> - > `(= (- 5 ,E 1!$ @! 6 !$ 6- 2 v$R U ,$!- ?= !$ + )B- ) !$ - :$ " .[23] 67 !$ ,D- Z !$ ?: 6- - + rV!U . #$ (C, 6 67 c- " `(= (- - 1\U C= <9 4!5 ;7 6Y! A[' #$ ! 67 !$ k,D- Z !$ @! . !> 2BBK ,- - D(G- )$ %! ) !$ @! $5 + #B <9 - !$ 6 67 :$ " 6- 9O\ H ,M . #$ (= + - ( ,$!- A0 B! !$ 6 aN>- !@ ,!,& 6B -9 W,> - - H 1!$ $5 + . F !$ @! )$!= :T9 ]JU H . [16] W! $ c- " `(= (- - !$ @! . 6 2:H <:E . ) [17] jBK W! ) 6 > #P& 5 . c- 5 = 7<' 4I9 " ?= #$ !$ H 7 ^C- )$!= Q ,9 - 6- $ "> " 2D(G- <:E 2BBK 1d9 649 . R( @"& !$ :t- 2H 6,> ^= - A0 :$ 4!:- 2 !$ @! !$ 6 67 :$ ^= - 1 W! 2J 0 Z :$ [20, <:E 2D(G- W! 6,,$ $ ,D- #$ . w- !$ @! + - 6 D(G- - !$ @! !$ $ 7 .21] + 6 6,= 2D(G- - C,>& , ,$ - ,D- #" 1 6$ " 6,,$Y>& H ,M #" !$ @! . ' - ! 67 :) :$ ^= . !$ @! !$ - + - L W! ' !$ EJO@5 + >& 2D(G- . Q)$ H !$ @! 3 ,$ - 2- 37<$ 37X<- 3 HDL !$ @! ! 67 1\U 1 #$ - U <$ U 4!:- 2 #" HDL )$& #$ . #" ,D- Z !,$ 67 K 67 ,$ - $ Z .[22] H @( - R(/&R( (D" $5 + \U D(G- .[26] ,D- S4!5 !$ + 6 > 2D(G- - ! 67 :) ,$ - !$ KO ;- )<7R c- ?= - -2- ,M #" - L . #$ !J Q 2- KO ;- Q . #$ !-& :C !$ :t- H #-= A= !J 2- dR ,!"7 E () K - C,>& , .,$- B R( )$& > W! . "\ !$ % C= -= ,M . 6J! !$ V 6,= !" #$ I" L"U :C ?: !$ + !$ + -2- D - C,>& 3 H $ ,0 1 Q)<7R 2 G\ ,M . Q)<7R ;- -u- c-

Q Horizon Med Sci Vol. 22, Iss. 3, Sum 2016 diabetes and its complications. Biomed Pharmacother. <7 <7 - #" !$ @! 2005;59(7):365-73. 7- Chen J, Zeng L, Xia T, Li S, Yan T, Wu S, et al. Toward a . 76 biomarker of oxidative stress: A fluorescent probe for (D" 39 - D(G- K- exogenous and endogenous malondialdehyde in living cells. Anal Chem. 2015;87(16):8052-6. V$ 1))$& ,- :$ )$!= ^= 8- Shaker ME, Houssen M, Abo-Hashem EM, Ibrahim TM. Comparison of , L-carnitine and melatonin in >- nZ - C,>& .$ 6 )$&<7 ameliorating carbon tetrachloride and diabetes induced " 3 )$ %! _:- a5 1= hepatic oxidative stress. J Physiol Biochem. 2009;65(3):225-33. . c- :$ 9- Petruzzella V, Baggetto LG, Penin F, Cafagna F, Ruggiero FM, Cantatore P, et al. In vivo effect of acetyl-L- carnitine on succinate oxidation, adenine nucleotide pool and lipid composition of synaptic and non-synaptic mitochondria from cerebral hemispheres of senescent 89 #$ !$ @! )B- !$ + rats. Arch Gerontol Geriatr. 1992;14(2):131-44. - + ,M . !> H H 10- Hajinezhad MR, Davari SA, Esmaeel Zadeh S, Miri HR, Akbari M. Protective effect of hydro alcoholic extract . O 6- from Prosopis farcta leaves on lipid peroxidation of serum and liver tissue in diabetic rats. J North Khorasan Univ Med Sci. 2015;7(2):267-78. [Persian] 3+ E= :) *+ 11- Ashraf H, Heydari R, Nejati V, Ilkhanipoor M. Preventive effect of berberis integerrima on the serum $- /)- E= -= :K- levels of glucose and lipids in streptozotocin (STZ)- .- > @ 6Y> Y>-= 2U ;& induced diabetes in rats. J Fasa Univ Med Sci. 2012;2(3):148-55. [Persian] <<( E % #P& @& :),- $ 12- Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides l45 !$ w- , Y>-= 2U - in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351-8. :, 6) 3+ ?T & 3<9 #P& 13- Hajinezhad MR, Esmaeel Zadeh Bahabadi S, Miri HR, Davari SA, Darvish Sargazi M. Effect of hydroalcoholic .(BP-QP-106-01 extract of Prosopis farcta pod on liver histopathology 7,) _ ",- 8D 7 :./ 01 and malondialdehyde level in streptozotocin diabetic rats. Horizon Med Sci. 2015;21(1):31-6. [Persian] . 6> 14- Yano H, Oyanagi E, Kato Y, Samejima Y, Sasaki J, Utsumi K. L-carnitine is essential to beta-oxidation of ^5 "U !$ -& % D(G- : ./ quarried fatty acid from mitochondrial membrane by 6> & 3<9 67 , PLA(2). Mol Cell Biochem. 2010;342(1-2):95-100. 15- Mahfouz MH, Ghanem HM, Mohamed MA. ."7 3+ @ 6Y> &3 Therapeutic effect of L-carnitine on sialic acid, soluble Fas (sFas) and other biochemical variables in hyperinsulinemic rats. Life Sci J. 2009;6(2):76-84. 16- Liu J, Head E, Kuratsune H, Cotman CW, Ames BN. Comparison of the effects of L-carnitine and acetyl-L- 1- Carlsson PO, Schwarcz E, Korsgren O, Le Blanc K. carnitine on carnitine levels, ambulatory activity, and Preserved β-cell function in type 1 diabetes by oxidative stress biomarkers in the brain of old rats. Ann mesenchymal stromal cells. Diabetes. 2015;64(2):587- N Y Acad Sci. 2004;1033:117-31. 92. 17- Maccari F, Arseni P, Chiodi. Levels of carnitines in 2- Panchal SK, Poudyal H, Ward LC, Waanders J, Brown L. brain and other tissues of rats of different ages: effect of Modulation of tissue fatty acids by L-carnitine attenuates acetyl-L-carnitine administration. Exp Gerontol. metabolic syndrome in diet-induced obese rats. Food 1990;25(2):127-34. Funct. 2015;6(8):2496-506. 18- Nascimento MA, Higa E, de Mello MT, Tufik S, Oyama 3- Parandak K, Arazi H, Khoshkhahesh F, Nakhostin- LM, Santos RV, et al. Effects of short-term l-arginine Roohi B. The effect of two-week l-carnitine supplementation on lipid profile and inflammatory supplementation on exercise-induced oxidative stress proteins after acute resistance exercise in overweight and muscle damage. Asian J Sports Med. 2014;5(2):123- men. Clin Nutr Espen. 2014;9(3):141-5. 8. 19- Ali SA, Faddah L, Abdel-Baky A, Bayoumi A. 4- Kobayashi A, Masumura Y, Yamazaki N. L-Carnitine Protective effect of L-carnitine and on treatment for congestive heart failure: Experimental and CCl4-induced liver injury in rats. Sci Pharm. clinical study. Jpn Circ J. 1992;56(1):86-94. 2010;78(4):881-6. 5- Cruciani RA, Dvorkin E, Homel P, Culliney B, Malamud 20- Heo YR, Kang CW, Cha YS. L-Carnitine changes the S, Shaiova L, et al. L-carnitine supplementation for the levels of insulin-like growth factors (IGFs) and IGF treatment of fatigue and depressed mood in cancer binding proteins in streptozotocin-induced diabetic rat. J patients with carnitine deficiency: A preliminary Nutr Sci Vitaminol. 2001;47(5):329-34. analysis. Ann NY Acad Sci. 2004;1033:168-76. 21- Irat AM, Aktan F, Ozansoy G. Effects of L‐carnitine 6- Rahimi R, Nikfar S, Larijani B, Abdollahi M. A review treatment on oxidant/antioxidant state and vascular on the role of antioxidants in the management of enhances Na(+), K(+)-ATPase -S-transferase reactivity of streptozotocin-diabetic rat aorta. J Pharm and multiple unit activity and reduces lipid peroxidation Pharmacol. 2003;55(10):1389-95. and lipofuscin concentration in aged rat brain regions. 22- Fernandez I, Tonietti M, Camberos MDC, Bergada I, Neurosci Lett. 2001;301(1):1-4. Schenone A, et al. Acetyl-L-Carnitine and nicotinamide 25- Kathirvel E, Morgan K, French SW, Morgan TR. for prevention of type 1 diabetes, I-literature review Acetyl-L-carnitine and improve mitochondrial which gave support to the treatment, II-case report, abnormalities and serum levels of liver enzymes in a evaluation of five years treatment. Immunome Res. mouse model of nonalcoholic fatty liver disease. Nutr 2015;11(2):094. Res. 2013;33(11):932-41. 23- Hino K, Nishikawa M, Sato E, Inoue M. L-carnitine 26- Aydogdu N, Atmaca G, Yalcin O, Taskiran R, Tastekin inhibits hypoglycemia-induced brain damage in the rat. E, Kaymak K. Protective effects of L-carnitine on Brain Res. 2005;1053(1-2):77-87. myoglobinuric acute renal failure in rats. Clin Exp 24- Kaur J, Sharma D, Singh R. Acetyl-L-carnitine Pharmacol Physiol. 2006;33(1-2):119-24.

Q Horizon Med Sci Vol. 22, Iss. 3, Sum 2016