Figure 12.1:Effect of Acute (one day) and Sub-chronic (fourteen days) Oral Administration of Methanol Extract of O. stamineus on Aminopyrine N-demethylase Activity in Young Female SD Rat Hepatocytes Results are analysed using Dunnett test; n=6; Value = mean±standard deviation.

Acute Oral Toxicity Study

During the experimental period, no lethality was seen within 24 hours post administration of methanol extract of O. stamineus. General observable toxic symptoms and adverse effects such as tremor, righting reflex and ataxia were not seen in normal young female SD rats. As seen in the Table 12.1, the serum urea, creatinine and total cholesterol levels of rats treated with 5 g/kg (P<0.01) of methanol extract of O. stamineus were significantly lower when compared to the control group. No significant changes in colour and relative organ weight i.e., liver, kidney, heart, spleen and lung was observed in normal young female SD post-24 hours of dose administration as compared to positive control group (Table 12.2).

The body weight, food consumption, water intake and relative organ weight of normal young female SD rats treated with extract did not show any significant change when compared to control group during the fourteen days recovery period (Tables 12.3 and 12.4).

Discussion

Although evidence obtained from human and animal experiments support the hypothesis that natural products promote health, it is possible that interactions with other modern drugs may override any subtle benificial effects of natural products in humans. Most reports of toxic effects due to the use of herbal medicines are associated with hepatotoxicity which ranged from mild elevations of liver enzymes to liver failure requiring liver transporting (Saad et al., 2006). The liver is the major organ responsible for the metabolism in most species (Gibson and Skett, 1994). The induction of hepatic metabolising enzymes plays a substantial role and has profound implications in clinical pharmacology especially metabolic interactions. In human liver the first step of biotransformation is mainly mediated by cytochrome P450 system. Among all isoforms of CYPs, CYP 3A4 needs particular attention in drug interactions. CYP 3A4 is involved in biotransformation of over 50 per cent of drugs in use today (Guengerich, 1996). For the safe use of methanol extract of O. stamineus, it is important to clarify CYP 3A4-mediated interaction between methanol extract of O. stamineus with the other modern drugs and the time course of methanol extract of O. stamineus-induced hepatic drug metabolising enzymes after a certain duration of treatment.

Model drug used in this study, aminopyrine is mainly N-demethylated by CYP P450 3A and 2B in rats and CYP 2C i.e., CYP 2C19 in humans although many other isoforms of cytochrome P450 are also involved (Kamataki, 1993; Timbrell, 2000). Aminopyrine N-demethylase enzyme is categorised as N-dealkylation reaction which belongs to one of the oxidation processes in the phase I hepatic drug metabolism reaction (Hodgson and Goldstein, 2001). Many natural compounds are identified as inhibitors or inducers for cytochrome P450 systems (Zou et al., 2002). Flavonoids induce direct stimulation of gene expression CYPs via a specific receptor e.g. aryl hydrocarbon receptor (AhR) or modulate enzymatic activities of CYP (Havsteen, 1983). As seen in Figure 12.1, it is suggested that methanol extract of O. stamineus may not cause any significant influence on the levels of CYP3A and CYP2B in normal young female SD rats which gave insignificant interaction with hepatic aminopyrine metabolism. The possible explanation could be due to the poor absorption of active chemical constituents in methanol extract of O. stamineus via gastrointestinal tract and are of insufficient amounts to possess significant interaction with the hepatic cytochrome P450 enzyme system in rats. Oral administration of rats with 15 mg/kg, 21 mg/kg and 5 mg/kg respectively of sinensitin, eupatorin and 3’-hydroxy-5,6,7,4’-tetramethoxyflavone has been reported to have a low absorption to about 10 per cent of sinensitin and below 2 per cent for both eupatorin and 3’-hydroxy-5,6,7,4’-tetramethoxyflavone (Loon et al., 2004). By prolonging the treatment of duration and increasing the dose may change the whole scenario.

Table 12.1: Effect of Oral Administration of O. stamineus Leaf Extract on Biochemical Parameters in Young Female SD Rats

Results are analysed using Dunnett test; n=10; Value = mean±standard deviation.

Negative control = Untreated SD rats.

Positive control = SD rats orally treated with distilled water only (vehicle-treated control group).

AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; TC: Total cholesterol

TAG: Triacylglycerol.

Stay updated, free articles. Join our Telegram channel

Join