Inhibitory Effects of Fruit Juices on Cytochrome - Research Paper Example

 Discussion Since the last 25 years, the study of food - drug interaction still goes on since the discovery that grapefruit juice inhibits cytochrome P450 (CYP3A4). As known that, Cytochrome P450 presents highly in the wall of the small intestine and in the liver. It oxidase substances in phase I metabolism. However, it was needed to be used in vitro experiment to examine this food – drug interaction, Procrine Esterase enzyme was used. It gives similar good reaction results as P450 do within less financial cost. Recently more Enzyme assay experiments has been done to define further other fruit juices interactions with drugs. Due to theses studies, a better understanding been gotten on how the drugs are metabolized, how they transported inside the body and how different natural products might affect metabolism and interaction processes. In the current investigations, GFJ was used as a control to investigate if other juices are inhibitor and to decide their type of inhibition by comparing their Km and Vmax. Vmax represents the maximum saturating substrate concentration rate achieved. Km (Michaelis-Menten constant) which is used to find the substrate concentration when the reaction rate is half Vmax. The effect of various fruits juices on the CYP3A4 activity by using esterase enzyme in vitro been evaluated in this study. Most juices were freshly squeezed in the laboratory. These juices were, Beetroot, Cherries, Grapefruit, Kiwi, Pineapple, Plum, Pomegranate, Raspberry and Sharron (Persimmons). Stored Pineapple juice was also examined. Among these fruits juices evaluated that the strongest inhibition of esterase activity was presence in the Stored pineapple juice as showed before in table 33. As a competitive inhibitor, it has the highest percentage in both Vmax and Km comparing with other juices. They were 34.76% decreasing in Vmax and 93.75% increasing in Km. The second higher inhibitory juice than GFJ was Cherries juice as a competitive inhibitor. There was 68% decreasing in Km, whereas, the second non-competitive inhibitor that has higher Vmax than GFJ was Beetroot juice. Although stored Pineapple juice is a nont-competitive inhibitor, the fresh juice was a competitive inhibitor. Pomegranate juice has no affect on esterase activity. There were no changes neither on Vmax nor Km. other competitive inhibitor juices are, Kiwi juice and Sharron Juice. On the other hand, Raspberry and Plum juices are other non-competitive inhibitors. However, GFJ with the addition of Honey is inhibit esterase enzyme competitively, there was around 19% less decreasing in Km. Nevertheless, there was mostly no changing in Vmax in both juices comparing with their control, there was 10.94% decreasing in GFJ Km whereas 9.84% increasing in GFJ+H. Perhaps, if the addition of honey was 1 tablespoon to the class of GFJ, the rate of Km might be less and therefore, inhibition of GFJ to Esterase enzyme will decrease; therefore, no inhibition will occur. Grape Fruit Juice (GFJ) Decisively, the interactions between food and drugs happen every day; however, the most significant aspect about the interaction is the alteration process of the total drug. Recent findings on the experimentation of the grapefruit juice show that it augments bioavailability of a few drugs in the mouth. On the other hand, according to the results from the laboratory experiment, GFJ has furanocoumarin products interfering with CYP3A4 as the key inhibitor. Decisively, the derivatives react with the esterase enzyme, which affects the comprehensive effects of the GFJ. The different derivatives from the juice entail bergapten, bergamottin, dihydroxybergamottin and bergaptol; moreover, they are all active furanocoumarins in the grape fruit juice (Kim 2006). Typically, CYP3A4 inhibitors are the most common in GFJ and they react with isoforms found in the liver hence multiple drugs have pre-systematic metabolism as the first process and the enzymes play this key role. However, a number of inhibitors found in the GJF also participate in the metabolism for drugs depending on the drug ingested but it is evident that the inhibition process augments their biological obtainability. Resolutely, the inhibition process takes up to three days but the effectiveness of the medication depends on the GFJ ingestion time. For the interaction of the grape fruit juice to be effectual, the ingestion should be four hours before taking the drug or with it. Beetroot Juice (BRJ) The Beetroot juice, as a non-competitive inhibitor has a different kind of inhibition properties and processes. The BRJ has phosphodiesterase inhibitors, such as sildenafil, vardanafil or tadalafil that form a foundation for the common claim that the juice has constituents that could reduce a human’s blood pressure (Green 2014). The beetroot, as a fruit has had different experiments in the past giving promising results about reacting with other enzymes; however, there lacks certainty on the effectual depths of its inhibitors. Essentially, the inhibitors found in BRJ react with the esterase enzyme in a period of 48hrs affecting the flow of blood. Typically, the phosphodiesterase inhibitors instigate the inhibition process by broadening the blood vessels hence making it easy for the blood to flow. Moreover, the inhibitors also interact with different constituents of the human blood to facilitate their effectiveness. Cherries Juice (CJ) Cherries juice is popular for its role in inflammation, which directly links with its inhibition process. The enzyme cyclooxygenase is the core inhibitor of CJ that has COX 1 and COX 2 as the core isoenzymes. Typically, cherries juice also inhibits both of them as expected for cyclooxygenase. The enzyme found in COX 2 is essential in the inhibition process since it eliminates pain besides the inflammation making it a prevalent inhibitor for the cherries juice (Kim 2006). Additionally, COX 1 serves a relative purpose that entails the formation of protective glands on the stomach walls but excessive ingestion of CJ can lead to their erosion hence leading to complications such as abscesses and haemorrhage Kiwi Juice (KJ) The Kiwi Juice has glycoprotein inhibitor of pectin methylesterase that holds an augmented affinity for the esterase enzyme; however, a rational argument is that the juice contains other inhibitors that react with different enzymes (Hidaka 2008). All the same, the pectin methylesterase is a protein that has vast acidic attributes and seems to be glycosylated. Kiwi Juice list of constituents under the PME inhibitor entails 3-methyl-2-butanone, 3-hydroxy-2-butanone, ethyl 3-hydroxybutyrate, phenyl ethyl alcohol among others but the KJ lacks any compounds that contribute to its flavour. Significantly, some people might say that the Kiwi, as a fruit, is more of a banana that has less compounds contributing to its saltiness or sweetness. This makes excess ingestion of the Kiwi juice a threat to comprehensive findings in the laboratory; especially within the first 36hrs because of the high interferences resulting from augmented urination. The inhibition process also has serotonin as more of a by-product that may also affect the analysis. Pineapple Fresh Juice (PAFJ) Unlike other juices, the pineapple juice has varying inhibition processes depending on its nature. Typically, specifying whether the juice is fresh or canned helps to some extent but does not entirely assist in establishing the PAFJ inhibitors. However, the results from methods applied in the experiment suggest that the core inhibitor found in PAFJ is protease. Protease is very prevalent in fresh pineapple juice unlike the canned and frozen where researchers had to add organic acids to establish the conclusive inhibitors (Ling 2001). Decisively, the inhibition activity reduces the harshness of irritation in the case of fresh pineapple juice unlike in frozen or canned pineapple juice where there lacks clarity whether the inflammation decreases or multiplies. Plum Juice In the recent past, plum juice has been subject to a lot of attention especially with the notion that it influences the fluids in the human blood. Essentially, the plum juice prompts cytotoxicity as angiotensin, one of the core inhibitors, amplifies the growth of muscles in the vascular system. Ingestion of plum juice guarantees that the inhibition process will regulate proteins in the system and the development of tumours (Frank 2002). Additionally, the plum juice’s inhibition process starts under 24hrs after consumption affecting the urinary system depending on the amount of consumption. High and moderate levels of consumption clear the urinary duct of any unnecessary reactions that cause the urine to have crystal-like substances; however, low consumption is very ineffective in this factor. Pomegranate Juice (PGJ) Definitely, Pomegranate juice has increased levels of tannin, a property that also contributes to PGJ inhibition process. Naturally, due to this factor, PGJ has anti-atherosclerotic attributes that play different roles in the human and animal bodies especially the elderly. For instance, the inhibition process of PGJ reduces the blood pressure courtesy of the antioxidants under the anti-atherosclerotic inhibitors (Dornfeld 2001). The PGJ inhibitors have demerits especially in cases of increased consumption where they affect the muscle form and physical performance in the elderly people. Pomegranate commonly applies as a negative and positive control in vivo studies for determining the inhibitors in other juices. Resultantly, a recent study where pomegranate juice applied as a control showed that human CYP3A, as an arbitrated breakdown, is one of its inhibitors. However, the pomegranate juice plays a significant part in food and drug interactions in rats by altering carbamazepine pharmacokinetics (Kim 2006). In conclusion, pomegranate juice inhibits human CYP3A activities but at potent levels smaller than other fruit juices such as black mulberry. Raspberry Juice Raspberry juice has non -competitive inhibitiors and when compared to other juices such as GJF, the process seems less complex. The juice has CYP3A inhibitors relative to the amount consumed; however, this is not easy to establish as for the GFJ, the prevalence stays at a minimum (Kim 2006). Typically, raspberry juice has significant inhibition similarities with the grape fruit juice; in addition to the CYP3A inhibitors, the RJ also has constituents such as catalysed midazolam 1 hydroxylation. Relatively, depending on the time and amount of consumption, the RJ inhibitors take part in drugs metabolism and prompts bioavailability. However, the results of raspberry depends on the studies applied in testing the inhibitors; for instance, raspberry juice requires substrates such as CYP3A as shown above, in the determination of the general inhibition activities. Moreover, the inhibition of midazolam 1’- hydroxylase activity in raspberry juice is not that prevalent like in other juices such as wild grape, grape fruit, black mulberry etc. However, it is still prevalent and ranks ahead of orange juice and plum juice that do not depict any inhibition on CYP3A activity (Kim 2006). Generally, components of commercial juices, inclusive of raspberry and grape fruit juice are inhibitors (basing on the mechanisms applied) of humanoid CYP3A action, particularly in vitro, and show a higher inhibitory potency as compared to pomegranate juice. References Dornfeld, L. 2001. Pomegranate Juice Inhibits Serum Angiotensin Converting Enzyme Activity and Reduces Systolic Blood Pressure: Journal of Atherosclerosis, vol.158, no.1: pp.195-98 Frank, G. 2002. Fruit Juice Concentrate of Plum Inhibits Growth Signals of Vascular Smooth Muscle Cells Induced by Angiotensin: Life Sciences, vol.72, no.6: pp.659-667 Green, S. 2014. Health Benefits of Beets: PATH, Retrieved 4th February 2015 from http://www.pathusa.org/blog/health-benefits-of-beets/ Hidaka, M. 2008. Inhibitory Effects of Fruit Juices on Cytochrome P450 2C9 Activity in Vitro: Journal of Bioscience, Biotechnology and Biochemistry, vol.72, no.2: 406-11 Kim, H. 2006. Inhibitory Effects of Fruit Juices on Cytochrome P4503A Activity: Department of Pharmacology and Pharmacogenomics Research Centre, Inje University College of Medicine, Korea, Retrieved 4th February 2015 from http://dmd.aspetjournals.org/content/early/2006/01/13/dmd.105.007930.full.pdf Ling, W, 2001. Pineapple Juice- Phenolic Consumption and Enzymatic Browning Inhibition: Oregon State University, Retrieved 4th February 2015 from https://ir.library.oregonstate.edu/xmlui/handle/1957/6720 Read More