Hepatoprotective Effect of Pomegranate: Histological Study

Hepatoprotective Effect of Pomegranate: Histological Study ORIGINAL ARTICLE A HISTOLOGICAL STUDY OF HEPATOPROTECTIVE EFFECT OF POMEGRANATE, IN MINOCYCLINE TREATED GUINEA PIGS Dr. M. Nadeem Siddiqui Dr. Sarwath Fatimee Dr. Hemant Kumar Dr. Bashir A. Sheikh ABSTRACT Objective: To determine the hepatoprotective effects of pomegranate on drug induced autoimmune hepatitis produced by minocycline. Material and Method: This experimental study was conducted in the department of anatomy, basic medical sciences institute, Jinnah post-graduate medical centre, Karachi. 30 adult male guinea pigs taken and divided in three groups, A, B and C, respectively with each group having 10 animals, Group A served as control, Group B was treated with minocycline 0.02mg/Gram body weight and Group C was given the minocycline along with pomegranate in the dose of 0.9 mg/ Gram body weight. On the completion of study, the animals were sacrificed and liver were removed for the histological examination under light microscopy in haematoxylin eosin staining. Results: The HE stained slides were studied and showed the normal architecture of liver in group A animals, distorted pattern of hepatic cords with marked infiltration of inflammatory cells in group B animals, and less altered pattern of hepatic cords with less infiltration of inflammatory cells in group C animals approximately similar architecture to control group. Conclusion: Use of pomegranate with minocycline can prevent hepatic damage particularly the autoimmune hepatitis. KEY WORDS: Minocycline, Pomegranate , hepatotoxicity , autoimmune hepatitis. INTRODUCTION Drugs are the most common cause of liver injury. More than 900 drugs toxins and herbs have been reported to cause liver injury.1 Drug induced autoimmune hepatitis (DIAH) has been reported to be caused by several drugs.2 Autoimmune hepatitis is a chronic inflammatory disease of the liver.3 marked by prominent infiltration of inflammatory cells.4it is an acute and potentially severe side effect, particularly often reported after the long term use of minocycline.5 A significant proportion of patients with autoimmune hepatitis have drug induced hepatitis, mainly because of this drug.6 Minocycline, a semi synthetic, broad spectrum antimicrobial tetracycline available since 1972 is widely prescribed as systemic antibiotic for acne vulgaris which is given for a prolonged period ( month to years).6 Foods rich in natural antioxidants have been proposed as a tool to prevent and cure liver damage.7 The pomegranate is one of the important dietary sources, that exhibits strong anti oxidant and an ti-inflammatory properties.8 Its main constitute, ellagic acid, have been proven to antagonize in vitro to inhibit the pro-inflammatory mechanisms.9 MATERIAL METHOD This experimental study was conducted for 8 weeks by taking 30 adult male guinea pigs of 450-650 weight at animal house of BMSI, JPMC, Karachi and divided them into three main groups i.e., A,B and C that comprises 10 animals each and receiving standard laboratory diet ad labitum. Group A served as control, group B was given minocycline 0.02 mg /G body weight / day orally based on human consumption for the duration of one year, while group C was given minocycline in the same dose along with pomegranate 0.9 mg /G body weight /day orally. At the end of the experimental period, all the animals were sacrificed under ether anesthesia and liver was removed to be fixed in 10% formalin for 24-48 hours. The tissue samples taken from the organ were then dehydrated in ascending strength of alcohol, cleared in xylene, infiltrated and embedded in paraffin wax. Tissue blocks were made and 4-5 ÃŽ ¼m thick sections were obtained by cutting them with microtome. The sections then mounted on glass slide s and were stained with haematoxylin and eosin. The morphological changes in normal architecture of liver lobule were observed under light microscope with the help of 8X ocular, 40X objectives and graded according to the infiltration of inflammatory cells within the three zones of hepatic lobule 8. The grading was done as follows: Grade O (normal N) : no infiltration of infiltration of inflammatory cells in any zone. Grade I (mild M+) : infiltration of inflammatory cells within zone I Grade II (moderate M++) : infiltration of inflammatory cells within zone II Grade III (marked M+++) : infiltration of inflammatory cells within zone III RESULTS The present study was design to observe the minocycline treated animal and pomegranate protected animal in guinea pigs. Observations and results of microscopic examination were compared with control animal. The minocycline treated group B animal showed the distorted pattern of hepatic cords, dilated central vein with marked congestion, and some swollen hepatocytes with piknotic nuclei. Areas of marked infiltration of inflammatory cells especially lymphocytes and plasma cells observed in zone III of hepatic lobule. The microscopic examination of pomegranate and minocycline treated group C animals showed the architecture of hepatic lobule in comparison to control group A that is less distorted of hepatic cords and less dilated central vein, while infiltration of inflammatory cells is markedly decreased and limited to zone I when compared to group B animals n: number of animals N: normal M+ : Mild. M+++ : Marked DISCUSSION The histological examination of hepatic lobules in haemotoxylin and eosin stained sections of control group A showed normal architecture as described by Young et al.10,11 In the minocycline treated animals of group B the architecture of hepatic lobule has markedly changed when compared to group A. It showed the irregular distorted pattern of hepatic cords, increase in vascularity and irregular shape of hepatocytes with pyknotic nuclei. This is in agreement with Lawrenson et al. who described the comparative changes in hepatic architecture after the use of minocycline that showed the necrotic and inflammatory changes with distorted pattern of hepatic cords.12 This is also concluded by Kumar et al. who also showed the necrotic changes and plasma cell infiltration with distorted pattern of hepatic cords in autoimmune hepatitis.13 Group C animals treated with pomegranate and minocycline simultaneously demonstrate the protective effects on hepatic architecture. The hepatic cords showed regular arrangement of and the hepatocytes were normal in shape, while the hepatic lobules showed less accumulation of inflammatory cells when compared to Group B animals. This is in accordance with the study of Novarro et al. who proved that after the treatment of pomegranate in hepatoma the pattern of distorted hepatic cords become normal.14 This is also in concurrence with the study of Middha et al. who concluded that utilization of pomegranate, ultimately improve the hepatic architecture by providing the protection against oxidative damage.15 CONCLUSION From the results of this study, it can be concluded that pomegranate has proved to be highly effective in preventing the hepatic damage produced by minocycline particularly minocycline induced autoimmune hepatitis. So use of pomegranate should be promoted in daily life, particularly in those patients who are on long term minocycline treatment. Figure 1: HE stained 4 micron thick sections of minocycline treated liver, showing dilated central vein (CV), distorted hepatic cords with numerous pyknotic nuclei (PN) and marked infiltration of inflammatory cells (IC). (Photomicrograph X400). Figure 2: HE stained section 4 micron thick of pomegranate protected in minocycline treated liver, showing less dilated central vein (CV), more regular hepatic cords (HC) with normal nuclei and less infiltration of inflammatory cells (IC). (Photomicrograph X 400). REFERENCES Mehta N, Ozick L. Drug-induced hepatotoxicity.Mar 28 2008, From http:// emedicine.medscape.com/article/169814.: Bjà ¶rnsson E, Talwalkar J, Treeprasertsuk S, Kamath PS, Takahashi N, Sanderson S, Neuhauser M, Lindor K. Drug-induced autoimmune hepatitis: clinical characteristics and prognosis. Hepatology. 2010 Jun;51(6):2040-8. Manns MP and Vogel A. Autoimmune Hepatitis, From Mechanisms to Therapy.  HEPATOLOGY2006;43:S132-S144. Aldenhoven M, van Enk JG, Avis WA. Czaja AJ. Minocycline-induced autoimmune hepatitis. Ned Tijdschr Geneeskd. 2013;157(3):A5465. Drug induced hepatitis with autoimmune features during minocycline therapy. Abe M, Furukawa S, Takayama S, Mlchitaka K, Mlnami H, Yamamoto K, Horiike N and Onji M.Internal Medicine. 2003; 42 (1): 48-52. Antioxidant activity and hepatoprotective effect of pomegranate peel and whey powders in rats. Ashoush IS, El-Batawy OI, El-Shourbagy GA. Annals of Agriculture Science ;2013: 58 (1): 27-32. Coursodon-Boyiddle CF , Snarrenberg CL,. Adkins-Rieck CK, Bassaganya-Riera J,2 Raquel Hontecillas R, Peter Lawrence P, Brenna JT, Jouni ZE, and DvorakB. Pomegranate seed oil reduces intestinal damage in a rat model of necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol. 2012 September 15; 303(6): G744–G751. Dell’Agli, M, Galli ,GV,Bulgari, M, Basillico, N, Romeo, S, Bhattacharya D, Taramelli, D, and Bosisio, E 2010, ‘Ellagitannins of the fruit rind of Pomegranate (Punica granatum) antagonist in vitro the host of inflammatory response mechanisms involved in onset of malaria’, Malaria journal, vol. 9, pp. 208. Young B, Lowe JS, Stevens A, Heath JW. Wheater’s Functional Histology ; A Text and Colour Atlas. 2006 :290-294. Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser SL, Jameson JL. Harrison’s Principles of Internal Medicine. 2005; 16th Edition: 1808. Lawrenson RA, Seaman HE, Sundstrom A, Williams TJ, Farmer RDT. Liver damage associated with minocycline use in acne. 2001;4: 333-349. Kumar V, Abbas AK, Fausto N, Mitchell RN. Robbins Basic Pathology.8th Edition. 2007; 8th Edition: 633. Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and Cotran Pathologic Basis of Disease. 2010; 8th  Edition: 855 Navarro M, Amigo-Benavent M, Mesias M, Baeza G, Gokmen V, Bravo L, Moralesa FJ. An Oxidative pomegranate seed extract ameliorates oxidative stress of human hepatoma HepG2 cells. Journal of Science of Food and Agriculture. 2014; 94: 162-167. Midha SK, Usha T, Pannde V. AReview on antihypergycemic and hepatoprotective activity of Eco-Friendly Punica Granatum peel waste. Evidence-Based Complementary and Alternative Medicine. 2013. From http://dx.doi.org/10.1155/2013/656172.

Pro/Con Paying College Athletets Essay

Even though paying college athletes may be fair in some people’s eyes, there are many negatives to this topic that could affect college sports for today’s athletes and the future of their sport. The NCAA and their colleagues all have different views and they vary from being supportive and backing up the idea, to being one hundred percent against it. No matter what type of fan it is and no matter what sport it is, there are positive and negative views on this argument and the variety of disagreement is astonishing. The most positive outlook on this is in most eyes would be that paying the athletes would be fair, and that they deserve at least some money. And even though that is without a doubt the most popular opinion, there are still many more. If the NCAA decides to pay the students, a good way to keep paying college athletes under control is by paying the student athletes for certain things, the key word is student. One plan is too pay the athlete as long as him or her maintains a certain grade point average. â€Å"If we want to reward college athletes and dramatically reduce the cheating that goes on in college sports, we should consider paying student athletes $1,000 per month during their four years of eligibility, providing they maintain a pre-determined grade point average† (Freeman, Marv). This plan would not only keep the student athletes in school, but it would make them do well and succeed in school. Even though some fans of pro sports may want to see a star player leave and go to the pros after one or maybe two years, education is still very important and so is graduating. This strategy would be a great motivator and would without a doubt grab the attention of the player’s parents. Another positive affect is that without a doubt the amount of money brought into colleges and universities would increase by large amounts because it would attract more student athletes to go to college. This plan could affect all levels of student athletes in a more than positive way; it could change the future of student athletes forever. The controversy on player’s safety is a very big issue in pro sports, but you don’t see nearly as much attention on it in college sports. There is no doubt that injuries occur more often in pro sports, but that doesn’t mean they don’t happen in college sports, and the NCAA really doesn’t protect their players very much at all. A solution to this is to have the players sign a contract for the college or university they attend. The contract would contain a variety of things, but the two most important things would be a certain amount of money and then a health care plan for the athlete. Lifetime of health insurance and benefits is very important to athletes, and remember not all student athletes go pro so they don’t have the luxury of pro sport health benefits. This plan would without a doubt make more players not only want to stay in college to receive these benefits, but it would also make student athletes want to attend a college and not have to worry about being disabled as an adult. Joe Branch, a great high school football player, told reporter Joe Nocera that he had turned down a scholarship to play football at Georgia Tech because, â€Å"I wouldn’t have had any shoulders left if I had played football in college.† This man turned down the opportunity of a lifetime because of the fact he knew he wouldn’t have health benefits for playing college football, so he had to give up his dream. This plan would be great for the NCAA and their athletes now and especially in the future. To every controversial topic there are positives, and there are negatives. In this case a huge problem is, where is all the money for the players going to come from? There truly is no answer for this, that’s why paying the athletes isn’t even close to becoming a done deal. According to Mike Higgins of USA today, only 20 NCAA division 1-football programs make a profit. And considering the fact that college football is the most popular NCAA sport, the number of other sport programs making a profit can’t be a very large number at all. Another question that can’t be answered is, do you pay all the athletes? There is no doubt that men’s basketball and football bring in the most money for their schools, athletically speaking, but you can’t only pay them. According to http://www.statisticbrain.com/ there are over 420,000 student athletes and combined in Division 1 and 2 there are 26 different types of athletic programs. The amount of student athletes and athletic programs makes it almost nearly impossible to have enough money to pay every single athlete male and female. This also puts small schools at a huge disadvantage. Schools like Notre Dame, Texas, Florida, Ohio State, and Alabama already have huge reputation advantages over small schools, but if the NCAA starts paying their athletes the bigger schools like the ones I mentioned will be able to offer so much more because schools like that already make more than enough money. Overall, this point in the argument really shows that if the NCAA starts paying their athletes it would truly take a  miracle to come up with that kind of money, and if they ever did come up with the money, it wouldn’t be fair to many schools across the country. One of the many reasons why the NCAA is considering paying their athletes is because they believe it will stop all the â€Å"under the table deals.† A solution like that will not stop corruption in the NCAA. That kind of solution is just the easy way out, and it won’t stop the people who offer the student athletes money, cars, jewelry, tattoos, etc. because those kind of people will stop at nothing. If the NCAA truly wants to put a stop to players accepting or being offered gifts they need to enforce more discipline. According to Todd Pheifer of Yahoo News, â€Å"Cam Newton was ultimately â€Å"exonerated† by the NCAA while at Auburn, there were stories of an $180,000 payment that was demanded by Newton’s father for Cam to attend Mississippi State.† A young and naà ¯ve student athlete would take that kind of offer without even hesitating because the amount of money the NCAA is offering to pay the student athletes, couldn’t even come close to that. Overall, the main point of this is that if the NCAA believes that paying their athletes a certain amount of money is going to stop the offers and the greediness, they are going to need to come up with a better plan then that. Even though paying college athletes may be fair in some people’s eyes, there are many negatives to this topic that could affect college sports for today’s athletes and the future of their sport. As we see here, there are many great controversial arguments on this topic. The cutting off of the athletes money if their grades slip, also the health care plan would not only help the reputation of the NCAA, but it would no doubt make the game safer and assure the student athletes a better future. On the other hand, we still have no idea where the money would come from and who would they give it to. In conclusion, I don’t believe the NCAA should pay their student athletes, even though it may seem like the fair and just thing to do, there are just too many negatives and downfalls to this argument and in the end would more than likely put many colleges and universities into debt.

The Cambodian Genocide And The Armenian Genocide - 2391 Words

The Cambodian Genocide and the Armenian Genocide have similar methods of how the victims were killed. They similarly murdered their victims, starved their victims and targeted government officials. They were different in that the Armenians were deported but the Khmer Rouge targeted Cambodians based of their class and had re-education camps. The Cambodian Genocide happened between 1975 and 1979 in Cambodia where the Khmer Rouge, a guerrilla group, over threw the government and started a regime to bring Cambodia back to year zero . The Khmer Rouge called this the Democratic Republic of Kampuchea . Their aim was to purify society from the influence of the west, and to create a communist country . The Khmer Rouge started this by destroying what was left of the old society and executing the wealthy, educated and military people. They banned all outside languages and religion. An estimated figure of 1.7 million Cambodians where killed during this period by the Khmer Rouge . The Armenian Massacre happened in 1894-1896 and the Armenian Genocide happened in 1915-1920 which was caused by the Turkish Government. The Turkish Government’s aim was to remove all the Armenians living in the Ottoman Empire because they were more educated and wealthier then the Turkish population . The Turkish Government was also worried that the Armenians would become allies with Russia, who were a threat to Turkey . They killed and deported the Armenians to prevent this happening. It has been estimatedShow MoreRelatedThe Armenian and Cambodian Genocides707 Words   |  3 PagesGenocide Paper The definition of genocide, according to the United Nations, was the attempt to destroy â€Å"a national, ethnic, racial, or religious group† by killing members, causing mental or bodily harm, harsh living conditions, prevention of births, and separating children from their families. There are four patterns of genocide, which do not always occur in every genocide since they’re not all the same. 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Social Anxiety Disorder The Various Forms Of Success

Social anxiety disorder is a mental disorder that many people struggle with each and every day. Social anxiety disorder, according to The Diagnostic and Statistical Manual of Mental Disorders, is defined and categorized as â€Å"a marked and persistent fear of one or more social/performance situations† (Vanin, Helsey Morgan,2008). It is the fear of being, or interacting, in social situations, which bring on feelings of self-consciousness and judgement from others. Social anxiety disorder, and many other anxiety disorders for that matter, go undetected, and therefore, unresolved. This leads to many people struggling with it their whole lives, which, in turn, causes problems when trying to achieve goals and being successful. Individuals who†¦show more content†¦Morrison, author of Re-Defining Success: Finding New Hope, â€Å"You don’t have to define success in the same way other people define success. In your current definition of success, you might see a landma rk of success as having a million dollars. But other ‘landmarks’ in your life can define your success, too. You can re-define success from the world’s definitions to whatever you believe is important to your life† (38). Success is personal and unique to each individual. In this paper, success will be looked at in more broad terms. We will look at success in relationships, friendships, as well as personal happiness, such as overcoming obstacles. Furthermore, this essay will also look into the ways putting hard work, effort and time into overcoming obstacles that the disorder throws in the way of people who struggle with social anxiety disorder. Unfortunately, this disorder is a mental disorder that can not easily be controlled by one’s self. It sometimes requires therapeutic and pharmaceutical actions in order to manage and overcome it, which, in a way, can be a success in itself. To begin, we will look at the way social anxiety disorder affects rela tionships. Research has proven that, overall, it is more difficult for individuals who suffer from social anxiety disorder to form, as well as maintain, relationships of all kinds, such as intimate relationships, friendships, and even relationships within the