depletion of GSH and hepatic injury (Tsukamoto and Lu 2001). It also helps in the

improvement of survival of animals in galactosamine-, acetaminophen- and

thioacetamide-induced liver damage and also in ischemia reperfusion-induced hep-

atotoxicity (Mato et al. 1997). Exogenous supply of SAM also decreased the liver

fibrosis in rats treated with CCl4 and also reduced the neoplastic hepatic nodules in

animal models of liver cancer (Mato et al. 1997; Pascale et al. 2002).

29.2.5 Thalidomide and Analogues

Thalidomide is derived synthetically from glutamic acid. It is also known as α-N-

phthalimidoglutarimide (Marriott et al. 1999). It was first synthesized in West

Germany by Chemie Grunenthal and sold under the name Contergan™which was

then licensed in 46 countries all over the world (Miller and Strömland 1999). It was

originally used as an antiemetic and sedative but was later associated to have birth

defects in the 1950s due to its teratogenic nature (Marriott et al. 1999). It has

potential therapeutic applications and has been widely used in various diseases

such as rheumatoid arthritis, angiogenesis, prurigo nodularis, Behcet’s disease and

discoid lupus (Marriott et al. 1999; Raje and Anderson 1999). It has been reported

that thalidomide is reported to possess anti-TNF-α and anti-inflammatory and

antifibrotic activities in the lungs and liver (Moreira et al. 1993; Raje and Anderson

1999; Fernández-Martínez et al. 2001, 2004; Muriel et al. 2003; Tabata et al. 2007;

Chong et al. 2006). CCl4-induced toxicity caused 33.3% mortality which was

reduced to 13.3% by thalidomide treatment. The serum biomarkers such as ALT,

γ-GTP and ALP were increased with CCl4 which were attenuated with thalidomide

treatment. Also, there was marked increased in lipid peroxides and abolished

glycogen in the liver by CCl4 which was prevented by thalidomide treatment. In

addition, significant improvement in liver collagen was also observed by thalido-

mide treatment (Muriel et al. 2003). However, thalidomide can be a good approach

for cirrhosis, but clinical studies are still lacking and require further studies.

29.2.6 Plant-Derived Hepatoprotective Agents

A wide variety of herbal remedies have been used for the treatment and management

of liver disorders or diseases. Most herbal therapies were discovered through the

folklore knowledge of tribal people, and some of these have laid the foundation of

basic research (Son et al. 2014; Sagar et al. 2014; Ali et al. 2018). Plant-derived

remedies are reported as the major source of hepatoprotection, and their isolated

bioactive compounds have been tested in many rodent-type animal models. Here, we

will discuss some selected medicinal plants and their isolated constituents evaluated

scientifically against liver disorders along with their mechanistic studies summarized

in Table 29.1.

29

The Pathophysiology of Liver Disorders and Pharmacotherapy Options with. . .

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