Hepatocyte Lysosomal Membrane Stabilization by Olive Leaves against Chemically Induced Hepatocellular Neoplasia in Rats

Abstract

Extensive efforts are exerted looking for safe and effective chemotherapy for hepatocellular carcinoma (HCC). Specific and sensitive early biomarkers for HCC still in query. Present work to study proteolytic activity and lysosomal membrane integrity by hepatocarcinogen, trichloroacetic acid (TCA), in Wistar rats against aqueous olive leaf extract (AOLE).TCA showed neoplastic changes as oval- or irregular-shaped hepatocytes and transformed, vesiculated, and binucleated liver cells. The nuclei were pleomorphic and hyperchromatic. These changes were considerably reduced by AOLE. The results added, probably for the first time, that TCA-induced HCC through disruption of hepatocellular proteolytic enzymes as upregulation of papain, free cathepsin-D and nonsignificant destabilization of lysosomal membrane integrity, a prerequisite for cancer invasion and metastasis. AOLE introduced a promising therapeutic value in liver cancer, mostly through elevating lysosomal membrane integrity. The study substantiated four main points: (1) the usefulness of proteolysis and lysosomalmembrane integrity in early prediction of HCC. (2) TCA carcinogenesis is possibly mediated by lysosomal membrane destabilization, through cathepsin-D disruption, which could be reversed by AOLE administration. (3) A new strategy for management of HCC, using dietary olive leaf system may be a helpful phytotherapeutic trend. (4) A prospective study on serum proteolytic enzyme activity may introduce novel diagnostic tools.

Olive leaf extract decreases age-induced oxidative stress in major organs of aged rats

“…The effective doses of OLE (approximately 500 and 1000 mg/kg bodyweight/day) were chosen according to previous studies. [24][25][26] In the current study, OLE, especially OLE 1000, was detected to diminish the high levels of hepatic MDA, DC and PC levels in aged rats. OLE treatments elevated GSH levels in the liver, but not the heart and brain.…”

“…In the present study, total OLE extract was used, and aged rats received OLE in drinking water for 2 months. The effective doses of OLE (approximately 500 and 1000 mg/kg bodyweight/day) were chosen according to previous studies . In the current study, OLE, especially OLE 1000, was detected to diminish the high levels of hepatic MDA, DC and PC levels in aged rats.…”

“…[11][12][13] Several experimental studies have shown that olive leaf extract (OLE) or its constituents, such as oleuropein, had protective effects in atherosclerosis, 14 diabetes, 15 hypertension, 16 cardiotoxicity, 17,18 neurotoxicity, 19,20 gastric lesions 21,22 and cancers. 23,24 OLE attenuated cardiac, hepatic and metabolic changes in rats with metabolic syndrome. 25 It prevented hepatic fat accumulation in a rat model of non-alcoholic steatosis, 26 and modulated cold restraint stress-induced oxidative changes in rat liver.…”

“…Several experimental studies have shown that olive leaf extract (OLE) or its constituents, such as oleuropein, had protective effects in atherosclerosis, diabetes, hypertension, cardiotoxicity, neurotoxicity, gastric lesions and cancers . OLE attenuated cardiac, hepatic and metabolic changes in rats with metabolic syndrome .…”

Trichloroacetic Acid Can Activate the Activity of Acidic Protease

“…It can also induce neoplasia (16) . On these occasions the used concentration of trichloroacetic acid ,such as 2-35%(m/V) , was usually very large.However, the researches on the influence of trichloroacetic acid of lower concentration on the activity of enzymes or the function of proteins seem fewer.So some preliminary researches on the theme with acidic protease from Asperigillus niger.…”