Impact of allyl disulfide on oxidative damage and liver regeneration in an experimental hepatectomy model

Abstract

Backgraund: We investigated the effects of allyl disulfide (a garlic extract) on tissue damage, regeneration, proliferation and oxidative damage in an experimental liver resection model. Materials and Methods: In the study, 24 female Wistar albino rats weighing approximately 200-250 g were used. Group 1: The rats in the experimental group all received a 70% hepatectomy and were fed an Allyl disulfide (30 µg/kg/day, Allyl disulfide, Sigma-Aldrich, formula: C6H10S2, CAS Number: 2179-57-9, formula weight: 146.27 g/mol) in supplement to a regular diet for 1 week both preoperatively and postoperatively. Group 2: The rats in the control group also underwent a 70% hepatectomy and were given regular food and water for 1 week both preop and postop. Group 3: In the sham group, all rats were sacrificed 7 days after surgery. For biochemical evaluation, SGOT, SGPT, bilirubin, CRP and MDA were studied. In a histopathological examination, the fattening of the liver tissue, existence of (macro-micro vesicular), fibrosis, pleomorphism at hepatocyte nuclei, portal inflammation, existence of intralobular inflammatory cells, dilation at sinusoids, congestion, congestion at the central vein, regeneration, existence of Kupffer cells in the sinusoidal lumen and ki-67 proliferation index at hepatocytes were examined. Results: A significant difference between group 1 and group 2 was observed regarding the existence of regeneration, (p:0.06), the occurrence of nuclear pleomorphisms (p:0,001) and the fibroblast activity status (p:0.001). Significant differences were found between the experimental groups in regard to Kupffer cell increase and dilation and the hyperemia status in the sinusoid lumens (p:0.013 and p:0.001, respectively). In the Allyl disulfide group, the proliferation index was significantly higher than that of the other groups (p:0,001), while the average plasma MDA value was lower than that of the other groups (p: 0,042). No significant differences were found among the groups with respect to tissue MDA values (p:0,720). No significant difference was found for SGPT (ALT) and SGOT (AST) levels between Group 1 and the other groups (p:0.247 and p:0.539, respectively). The average total bilirubin (T. Bili) values were 0,12, 0,08 and 0,04 in the allyl disulfide group, control group and Sham group, respectively. This difference among the groups is statistically significant (p:0.001). The average direct bilirubin (D. Bili) values were 0,06, 0,02 and 0,02 in the allyl disulfide group, control group and Sham group, respectively. This variation among the groups is also statistically significant (0.001). Conclusion: We observed that the use of Allyl disulfide supplementation after major hepatectomy has a positive impact on liver regeneration, proliferation and oxidative damage. Abbreviations: Postop: post-operative, Preop: pre-operative, SGOT(AST): serum glutamic oxaloacetic transaminase, SGPT(ALT): serum glutamate-pyruvate transaminase, CRP: C- Reactive protein, MDA: Malondialdehyde, DAS: Garlic extract diallyl sulfide, AGE: aged garlic extract.Date generale: Am investigat efectele disulfurii de alil (un extract de usturoi) asupra distrucåiei tisulare, regenerãrii, proliferãrii æi distrugerii oxidative pe un model experimental de rezecåie hepaticã. Materiale æi metode: În acest studiu 24 de femele de æobolani albi Wistar cu greutãåi de aproximativ 200-250 g au fost utilizaåi. Grupul 1: toåi æobolanii din acest grup experimental au fost supuæi unei hepatectomii de 70% din dimensiunea ficatului æi au fost hrãniåi cu disulfurã de alil (30 ?g/kg/zi, disulfurã de alil, Sigma-Aldrich, formula: C6H10S2, NumãrulCAS: 2179-57-9, greutate molecularã: 146.27 g/mol) suplimentar faåã de dieta normalã timp de câte o sãptãmânã pre- æi postoperator. Grupul 2: Æobolanii din grupul control au fost de asemenea supuæi unei hepatectomii în proporåie de 70% æi au primit un regim nutriåional æi de hidratare normale atât pre-, cât æi postoperator. Grupul 3: În grupul de control non-placebo toåi æobolanii au fost sacrificaåi la 7 zile dupã intervenåia chirurgicala. În vederea evaluãrii biochimice, AST, ALT, bilirubina, CRP æi malondialdehida sericã au fost studiate. În cadrul analizei histopatologice au fost examinate acumularea de åesut grãsos la nivel hepatic, existenåa fibrozei (macro-micro veziculare), pleomorfismul nucleilor hepatocitelor, inflamaåia portalã, existenåa de celule inflamatorii intralobulare, dilatarea la nivelul sinusoidelor, congestia, congestia venei centrale, regenerarea, existenåa de celule Kupffer în lumenul sinusoidal æi indicele de proliferare ki-67 la nivelul hepatocitelor. Rezultate: S-a observat o diferenåã semnificativã între grupurile 1 æi 2 în ceea ce priveæte prezenåa regenerãrii, (p:0.06), pleomorfismelor nucleare (p:0,001) æi statusului de activitate fibroblasticã (p:0.001). Diferenåe semnificative au fost gãsite între grupurile experimentale vizând creæterea numericã æi dilatarea celulelor Kupffer æi statusul hiperemic la nivelul lumenelor sinusoidelor (p:0.013 æi p:0.001 respectiv). În grupul cu administrare de disulfurã de alil indicele de proliferare a fost semnificativ mai ridicat decât în celelalte grupuri (p:0,001), în timp ce valoarea medie a malondialdehidei serice a fost mai scãzutã comparativ cu celelalte 2 grupuri (p: 0,042). Nu s-au înregistrat diferenåe semnificative între grupuri referitor la valorile de malondialdehidã tisularã (p:0,720). Nu s-au gãsit diferenåe importante între nivelurile de ALT æi AST din grupul 1 în comparaåie cu celelalte grupuri (p:0.247 æi p:0.539 respectiv). Valorile medii de bilirubinã totalã au fost de 0,12, 0,08 æi 0,04 în grupurile 1, 2 æi 3. Aceastã diferenåã dintre grupuri prezintã semnificaåie statisticã (p:0.001). Valorile medii ale bilirubinei directe au fost 0,06, 0,02 æi 0,02 în grupul experimental, grupul control æi grupul control non-placebo. Æi aceastã variaåie între grupuri este semnificativã din punct de vedere statistic (0.001). Concluzii: Am observat cã suplimentarea de disulfurã de alil dupã o hepatectomie majorã are un impact pozitiv asupra regenerãrii, proliferãrii æi distrugerii oxidative la nivel hepatic.