1. Introduction
The liver is an auxiliary organ of the digestive tract. It fulfills many functions that are essential to life. It participates in the process of digestion through biliary secretion. All substances introduced into the body reach the bloodstream to be transformed before being excreted. Thus, the liver is exposed to various aggressions which sometimes have serious damages on the organism. It has been estimated in recent reports that 10% of world population is affected with liver diseases including hepatitis. Morbidity and mortality resulting from liver diseases is a major public health problem worldwide [1] .
Drug-induced hepatitis is manifested by inflammatory processes. These data show that liver disease is a public health problem in the world. It is important that some to improve the prevention and treatment of liver disease through scientific research. The availability of a varied plants repertoire with hepatotropic action in the traditional medicine of Burkina Faso [2] and the hepatic damage linked to Paracetamol exposure motivated this study. Sarcocephalus latifolius is a medicinal plant whose different parts are used to treat various diseases in Burkina Faso. The fruits are edible and remain an excellent source of nutrients in vitamins, minerals as well as carbohydrates [3] . Likewise, fruit of Sarcocephalus latifolius is used in traditional medicine for the treatment of many diseases [4] . These roots and fruits are used to treat liver disease and jaundice [5] . The objective of the study was to evaluate the hepatoprotective activity of the aqueous extract of the fruits of Sarcocephalus latifolius on paracetamol-induced hepatotoxicity in rats.
2. Materiel and Methods
2.1. Plant Collection
The fruits of the Sarcocephalus latifolius plant were collected in the South West region of Burkina Faso. A specimen (18,028) was deposited in the Herbarium of the Département de Botanique de l’Université Joseph KI ZERBO, Ouagadougou (Burkina Faso). The collected fruits were washed with water, cut into small parts and dried in the shade without dust for a week and pulverized.
2.2. Plant Extraction
These dried fruits were pulverized and 400 g of this powder were macerated in 1000 ml of distilled water for 24 hours. The filtrate was centrifuged at 2000 rpm for 10 min. The supernatant was frozen at −23˚C and lyophilized. Aqueous extract of Sarcocephalus latifolius fruits (EASL) obtained, was stored at −4˚C. The extraction yield was 24.23%.
2.3. Experimental Animals
Thirty male Wistar rats weighing between 150 and 200 g were randomized into six groups of five rats. Rats were maintained under standard laboratory conditions (temperature: 22˚C ± 3˚C, relative humidity: 50% ± 10% and light/dark cycle: 12/24h). Food pellets and water were provided ad libitum. The animals were used in accordance with the local ethic committee of Université Joseph KI-ZERBO.
2.4. Paracetamol-Induced Hepatotoxicity in Rat
Rats were randomized into six groups of rats including five rats for each group. The treatments were achieved according to the experiment design described by [6] [7] :
Group I (Vehicle): Rats received 0.9% NaCl solution at 0.5 mL/rat with normal diet.
Group II (Negative control): Rats received paracetamol at 1 g/kg bw (p.o.)
Group III (Positive control): Rats received Silymarin at 50 mg/kg bw (p.o.)
Group IV: Rats received paracetamol 1 g/kg bw, (p.o.) and aqueous extract of Sarcocephalus latifolius fruit 100 mg/kg bw (p.o.)
Group V: Rats received paracetamol 1 g/kg bw, (p.o.) and aqueous extract of Sarcocephalus latifolius fruit 250 mg/kg bw (p.o.)
Group VI: Rats received paracetamol 1 g/kg bw, (p.o.) and aqueous extract of Sarcocephalus latifolius fruit 500 mg/kg bw (p.o.)
2.5. Biochemical and Histopathology Studies
On day 8, rats were anesthetized with ether, sacrificed, and blood was collected centrifuged at 3000 rpm during 15 minutes for serum separation. Serum was stored at −20˚C until biochemical studies. The change in aspartate amino transferase (ASAT), alanine amino transferase (ALAT), alkaline phosphatase (PAL), and total bilirubin (TB) levels were measured for biochemical investigations. Atlas diagnostic product kits were used for these investigations.
Then animals were sacrified and livers were removed weighed. The liver samples were washed with saline, fixed in 70% ethanol and were processed for paraffin embedding following the microtome technique. The sections were taken at 5 μm thickness processed in alcohol-xylene series and were stained with alum-haematoxylin and eosin. The sections were examined microscopically for the evaluation of histopathological changes.
2.6. Statistical Analysis
Results were expressed as Mean ± SEM, (n = 5). Statistical analyses were performed with one-way analysis of variance (ANOVA I) followed by Tukey’s multiple comparison test by using Graph Pad Prism Software. P < 0.05 was considered to be statistically significant.
3. Results and Discussion
3.1. Results
3.1.1. Effect of Aqueous Extract of Sarcocephalus latifolius Fruit on the Body Weight Gain and Liver Weight in Paracetamol-Induced Hepatotoxicity in Rats
Extract caused a non-significant (p > 0.05) weight gain in the rats compared to the negative control. The extract did not cause a significant (p > 0.05) change in liver weight compared to the control (Figure 1).
3.1.2. Effect of Aqueous Extract of Sarcocephalus latifolius Fruit on Transaminases Levels in Paracetamol-Induced Hepatotoxicity in Rats
The extract at all doses significantly (p < 0.05) decreased ALAT level compared to the negative control. Extract at the dose of 500 mg/kg had the best percentage protection against paracetamol-induced hepatotoxicity. It was about 44% (Figure 2).
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Key: Para: Paracetamol; Silym: Silymarin.
Figure 1. Effect of aqueous extract of Sarcocephalus latifolius fruit on the body weight gain and liver weight in paracetamol-induced hepatotoxicity in rats.
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Key: Para: Paracetamol; Silym: Silymarin. #: Comparison of the different groups with the neutral control (NaCl 0.9%). *: Comparison of the different groups with the negative control (Para 1000 mg/kg).
Figure 2. Effect of aqueous extract of Sarcocephalus latifolius fruit on ALAT level in paracetamol-induced hepatotoxicity in rats.
Paracetamol induced a significant (p < 0.05) increase in ASAT levels compared to neutral control. Extract at all doses induced a significant decrease in the level of this enzyme compared to the negative control. Extract 500 mg/kg showed a better percentage of hepatocyte protection (Figure 3).
3.1.3. Effect of Aqueous Extract of Sarcocephalus latifolius Fruit on Total Bilirubin Level in Paracetamol-Induced Hepatotoxicity in Rats
Paracetamol induced a significant (p < 0.001) increase in total bilirubin levels compared to the neutral control. Extract at all doses induced a significant (p < 0.001) decrease in bilirubin level compared to the negative control. The extract protected liver cells at 45%; 40% and 63% for the doses of 100, 250 and 500 mg/kg, respectively (Figure 4).
3.1.4. Effect of Aqueous Extract of Sarcocephalus latifolius Fruit on Alkaline Phosphatase Level in Paracetamol-Induced Hepatotoxicity in Rats
Paracetamol induced a significant (p < 0.001) increase in alkaline phosphatase levels compared to the neutral control. Extract at all doses induced a significant (p < 0.001) decrease in alkaline phosphatase level compared to the negative control. The extract protected liver cells at 66%, 70% and 73% for the doses of 100, 250 and 500 mg/kg, respectively (Figure 5).
3.1.5. Histopathological Evaluation of the Effect of Sarcocephalus latifolius and Vehicles Groups in Paracetamol-Induced Hepatic Injury in Rats
Histopathological profiles showed a hepatoprotective activity of the aqueous extract of Sarcocephalus latifolius fruits at all doses. However, animals only treated with paracetamol showed hepatocellular and centrilobular necrosis. This necrosis was accompanied by leukocyte infiltration in the liver. There were also
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Key: Para: Paracetamol; Silym: Silymarin. #: Comparison of the different groups with the neutral control (NaCl 0.9%). *: Comparison of the different groups with the negative control (Para 1000 mg/kg).
Figure 3. Effect of aqueous extract of Sarcocephalus latifolius fruit on ASAT level in paracetamol-induced hepatotoxicity in rats.
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Key: Para: Paracetamol; Silym: Silymarin. #: Comparison of the different groups with the neutral control (NaCl 0.9%). *: Comparison of the different groups with the negative control (Para 1000 mg/kg).
Figure 4. Effect of aqueous extract of Sarcocephalus latifolius fruit on total bilirubin level in paracetamol-induced hepatotoxicity in rats.
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Key: Para: Paracetamol; Silym: Silymarin. #: Comparison of the different groups with the neutral control (NaCl 0.9%). *: Comparison of the different groups with the negative control (Para 1000 mg/kg).
Figure 5. Effect of aqueous extract of Sarcocephalus latifolius fruit on alkaline phosphatase level in paracetamol-induced hepatotoxicity in rats.
vascular congestion leading to destruction of the sinusoidal canaliculi and hepatic arteries. The inflammation of the hepatocytes was less severe or even reduced in the groups treated with the 500 mg/kg extract, as well as in the groups treated with Silymarin 50 mg/kg (Figure 6).
3.2. Discussion
Paracetamol is sometimes used as an analgesic and antipyretic. When taken in overdose (at least 200 mg/kg), Paracetamol can produce significant hepatotoxic effects [8] . In the liver, there is a protective mechanism involving glutathione in the regression of cellular damage [9] . But when paracetamol is used in high doses, the glutathione level is not sufficient to conjugate N-acetyl-p-benzoquinoneimine (NAPQI). Therefore, NAPQI alkylates the proteins present in the biomembranes of microsomes and mitochondria, producing hepatic necrosis [10] [11] [12] . Therefore, macromolecules such as enzymes will pass from the damaged tissues into the bloodstream [13] and the study of the activity of these enzymes in plasma is very important for the assessment of liver injury [14] . Increased ASAT and ALAT level indicates cellular damage and loss of functional integrity of hepatocytes [15] .
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Key: CV: central vein; HA: hepatic artery, H: hepatocytes; VC: vascular congestion; CS: sinusoidal canaliculus, NHC: hepatocellular necrosis; IC: inflammation cell, Ht: hematite.
Figure 6. Histopathological evaluation of the effect of Sarcocephalus latifolius and vehicles groups in paracetamol-induced hepatic injury in rats (H & E × 400). (a) treated with normal saline; (b) treated with Paracetamol; (c) treated with Silymarin 50 mg/kg; (d) treated with aqueous extract of Sarcocephalus latifolius fruit (100 mg/kg); (e) treated with aqueous extract of Sarcocephalus latifolius fruit (250 mg/kg); (f) treated with aqueous extract of Sarcocephalus latifolius fruit (500 mg/kg).
Increased PAL in liver disease reflects pathological alteration of bile flow [16] .
The abnormally high serum level of ALAT, ASAT, PAL and total bilirubin observed in the negative control group is a consequence of paracetamol-induced liver dysfunction and indicates liver cell damage. The extract at doses of 100,250, and 500 mg/kg significantly (p < 0.01) decreased the activity of ASAT and ALAT compared with the negative control. The increase in serum PAL could be due to its high synthesis following high bile pressure. The extract at all doses showed a highly significant reduction in PAL and bilirubin levels in the test groups. These results were comparable to those of the standard drug, Silymarin. The extract appears to offer protection and maintain liver cell function. Extract of Sarcocephalus latifolius fruits possesses flavonoids and tannins recognized for their hepatoprotective action. Saponins, alkaloids, flavonoids, phytates and triterpenoids are phytochemical constituents of Sarcocephalus latifolius with antioxidant, free radical scavenging and peroxidant inhibition capacity and inhibition of lipid peroxidation. These results are comparable to those of [7] [17] [18] [19] . Silymarin isolated from Silybum marianum has a protective effect on the plasma membrane of hepatocytes and has multiple inhibitory effects against different hepatotoxic agents. The antioxidant effects and the regenerative functions of Silymarin cells involve protein synthesis, which has been considered as the most important actions of Silymarin. The hepatoprotective activity observed in the present study may be due to the protective effect of Sarcocephalus latifolius on the plasma membrane of hepatocytes or cells regeneration function similar to that of Silymarin. These results are comparable to those [7] [20] .
The histopathological results showed that Sarcocephalus latifolius extract exhibited good protection on the architecture of the liver. Paracetamol could have an inflammatory effect by inducing the release and action of endogenous pro-inflammatory mediators responsible for the development of inflammation. The aqueous extract of Sarcocephalus latifolius fruits could show an anti-inflammatory effect by preventing the release of endogenous pro-inflammatory mediators responsible for inflammation [21] . The extract of Sarcocephalus latifolius fruits could block the degradation of arachidonic acid by the cyclooxygenase or lipo-oxygenase pathway. It would thus oppose the production of prostaglandins, thromboxane A2 and also leukotrienes [22] . This protection was almost to the liver of rats treated with Silymarin. These results validate the hepatoprotective effect of the aqueous extract of Sarcocephalus latifolius fruits on paracetamol-induiced hepatotoxicity.
4. Conclusion
These results validate the hepatoprotective effect of the aqueous extract of Sarcocephalus latifolius fruits on paracetamol-induced hepatotoxicity. By applying the appropriate dose and orally, the aqueous extract of Sarcocephalus latifolius fruits constitutes a good hepatoprotective drugs. But it would be important to evaluate the activity of aqueous extract of Sarcocephalus latifolius fruits on oxidative stress parameters in vivo in rats. Also it would be interesting to isolate the bioactive compounds found in the fruits of Sarcocephalus latifolius to confirm its use in traditional medicine.