Protective Effects of Garlic Oil on Hepatocarcinoma Induced by N-Nitrosodiethylamine in Rats

Abstract

To investigate the protective effects and the possible mechanisms of garlic oil (GO) against N-nitrosodiethylamine (NDEA)-induced hepatocarcinoma in rats, Wistar rats were gavaged with GO (20 or 40 mg/kg) for 1 week, and then were gavaged with GO and NDEA (10 mg/kg) for the next 20 weeks. The changes of morphology, histology, the biochemical indices of serum, and DNA oxidative damage of liver were examined to assess the protective effects. Lipid peroxidation (LPO), antioxidant defense system, and apoptosis-related proteins were measured to investigate potential mechanisms. At the end of the study (21 weeks), GO administration significantly inhibited the increase of the nodule incidence and average nodule number per nodule-bearing liver induced by NDEA, improved hepatocellular architecture, and dramatically inhibited NDEA-induced elevation of serum biochemical indices (alanine aminotransferase , aspartate aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase) and hepatic 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in a dose-dependent manner. The mechanistic studies demonstrated that GO counteracted NDEA-induced oxidative stress in rats illustrated by the restoration of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST) levels, and the reduction of the malondialdehyde (MDA) levels in liver. Furthermore, the mRNA and protein levels of Bcl-2, Bcl-xl, andβ-arrestin-2 were significantly decreased whereas those of Bax and caspase-3 were significantly increased. These data suggest that GO exhibited significant protection against NDEA-induced hepatocarcinogenesis, which might be related with the enhancement of the antioxidant activity and the induction of apoptosis.

Effects of Garlic Oil on Pancreatic Cancer Cells

“…Recently, it has been gradually understood that the latter are responsible for anticancer effects exerting through multiple mechanisms such as: amelioration of oxidative stress and improvement of immune function (Butt at al., 2009), and inhibition of metabolic carcinogenic activation (Miroddi at al., 2011;Velliyagounder et al, 2012;Wang et al, 2012;Zhang et al, 2012) Experiments in further had shown new mechanisms for the anticancer role of garlic oil such as by inducing apoptosis (Choi and Park, 2012;Wang et al, 2012), inhibiting differentiation, inhibiting tumor angiogenesis (Konkimalla et al, 2008), and reversing multidrug resistance (Arora et al, 2004). As compounds, it has been demonstrated that garlic oil has the ability to enhance the absorption of its main active component (Amagase et al, 2001).…”

“…How garlic oil exhibits its effect on the tumor cells and its underlying mechanism are poorly understood (Agarwal at al., 2007;Zhang at al., 2012), especially the effect on pancreatic carcinoma. For this reason, the aim of this study is to investigate the effect of garlic oil on human pancreatic cancer cells (including AsPC-1, PANC-1, and Mia PaCa-2 cell lines) and its underlying mechanism in order to find a pathway for pancreatic cancer prevention and treatment considering its multidrug resistance.…”

Aloperine Protects Mice against Ischemia-Reperfusion (IR)-Induced Renal Injury by Regulating PI3K/AKT/mTOR Signaling and AP-1 Activity

“…Given that tubular cells are very susceptible to ROS (20)(21)(22), renal tubular apoptosis is a characteristic feature for the progression of IR insult (23).…”

Ultrapathological evaluation of the anticancer effect of blackseed (Nigella sativa) and garlic (Allium sativum) in mice

“…Many investigations are now being carried out to discover naturally occurring compounds which can suppress or prevent the process of carcinogenesis. 3,4 Epidemiological studies continue to support the premise that dietary intake of Allium vegetables such as garlic may reduce the risk of different types of malignancies, included tumors of the liver, 5 lung, 6 skin, 7 stomach in rodents. 8 The protective effect against cancer of Allium vegetables is attributed to organosulfur compounds (OSC) including diallyl sulfide, diallyl disulfide (DADS), and/or diallyl trisulfide (DATS).These compounds have an immunomodulatory effect.…”

“…These findings were similar to those obtained by Khan and Sultana,31 who recorded that Nigella sativa is a potent chemopreventive agent and suppresses Fe-NTA-induced oxidative stress, hyperproliferative response and renal carcinogenesis in Wistar rats. Garlic and its allyl sulfur may exert their protective effects on carcinogenesis in animal and in vitro by several mechanisms, including inhibition of carcinogen-induced DNA adduct formation, 32 blockage of cell growth, blockage of cell proliferation, and blockage of angiogenesis, 33 induction of differentiation and/or apoptosis, 5,34 enhancement of carcinogen-detoxifying enzymes, 35 and/or suppression of carcinogenactivating enzymes, 36 inhibition of cyclooxygenase-2 expression, 37 scavenging carcinogeninduced free radicals, 38,39 and inhibition of lipid peroxidation. 39,40 Another possible mechanism of cancer prevention and suppression of cancer progression is immune enhancement by garlic, 9 and Nigella sativa, 21 and these agreed with our hematologic and histopathological findings.…”