Special Section | Histology of normal tissues | Original Research Open Access

Ultrastructure and Pathology Study of the Effect of an Antidepressant (Olanzapine) on the Health of Mitochondria in liver of male Albino Rat

Nafisa Mohammad Batarfi

Biology Department, Faculty of Science, University of Jeddah, Sao Tome and Principe.

*Correspondence: nmbatarfi@uj.edu.sa

AbstractBackground: Depression is one of the most common diseases in the last period, and it is a psychological disease that affects different age groups. In a scientific study conducted in the United States, the prevalence of it was large and expected to spread in other countries, which made it a catalyst for many doctors to do many studies that depend on the effect of sedative drugs (Andrade L, et al., ( 2003)). Olanzapine is considered an anti-depressant medication and may have a direct impact on the body’s organs in general. Therefore, many studies have examined the harm of taking sedative drugs and the possibility of studying changes or side effects to them and the possibility of treatment where many studies indicated the impact of the liver by it, as the liver is the first organ in the process of filtering the body from toxins with fatty tissue.Methods: The study was conducted on 50 male white rat (Albino rat) and divided into groups. The first group: (10) rats, the negative group that fed the standard meal, the second group: (10) rats, the treatment group that was given a dose of ZYPREXA at a rate of 6 mg/kg/day for eight weeks orally by the gastric tube. The dissection was carried out, a sample was taken from the liver and placed in the anthrax-stabilizer “primary stabilizer”, then placed in osmium and the steps followed for electronic microscopy were followed (Bancroft & Stevens, (1996)). Results: When examining the micro-structural sectors of the liver tissue, pathological changes in the hepatic sectors appeared from their normal form, with blood stasis, bleeding and inflammation of the hepatic cells. Acute deformation of the hepatocytes and mitochondrial degeneration and change in its forms with the fragmentation of the rough endoplasmic reticulum and the abundance of the smooth endoplasmic reticulum, a large number of caper cells and phagocytic cells, hematuria, the emergence of collagen fibers and deformation in the portal area and bile ducts.Keywords: Zyprex, Liver, Sinusoid, Kupffer cell, I to cell, hepatocytes

© 2020 Nafisa Mohammad Batarfi; licensee Herbert Publications Ltd. This is an Open Access article distributed under the terms of Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0). This permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

IntroductionDepression is a common disease these days and it is a mental illness that affects people of all ages and it is a very common disorder among the general public. In a scientific study con-ducted in the United States, it was found that the prevalence of the disease was 16.9%, and it is expected that it will spread in the world at higher rates which led many doctors of the International Epidemiology Federation to study the effect of sedatives as people treat them as a treatment for depression

[1]. Antidepressants are known to have negative effects. The effects of antipsychotics on the second generation are high on metabolic syndrome and may have harmful side effects on body parts such as the liver. These are the filtration organs responsible for developing the effects of antidepressants. Medi-cines increase the production of sugar in the liver by activating adenosine and activating protein kinase in the hypothalamus in the brain, which activates the presence of Olanzapine, which leads to high blood sugar [2].

Journal of Histology & HistopathologyISSN 2055-091X | Volume 7 | Article 3

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doi: 10.7243/2055-091X-7-3Nafisa Mohammad Batarfi, Journal of Histology & Histopathology 2020, http://www.hoajonline.com/journals/pdf/2055-091X-7-3.pdf

Materials and methodsAnimals- The study will be conducted on the males of the white rats (Albino rat) 20 Control Group: (10) the rats of the negative group who feed on the standard meal.

- The second Treatment group: (10) treated with Zyprex dose at 6 mg/kg/day for 8 weeks by mouth via stomach tube for four weeks by the gastric tube.

ChemicalsDrug: Zyprexa is used as an antidepressant Effect of black bean on the immune system: Studies and scientific research mention that the black bean has a stimulating effect on im-mune functions and this effect has been shown to improve the effectiveness of natural killer cells and these results can be of great therapeutic importance in the prevention of cancer , liver viruses and cases associated with deficiency in immune system.

Ultrastructure Studies- The study will be conducted on the males of the white rats (Albino rat) 20 Control Group: (10) the rats of the negative group who feed on the standard meal.

- The second Treatment group: (10) treated with Zyprex dose at 6 mg / kg / day for 8 weeks by mouth via stomach tube for four weeks by the gastric tube.

Results Control group (Figure 1-6).Treatment Group (Figure 7-22).

DiscussionOlanzapine is an antidepressant, which has a strong effect on the liver when ingested, as previous studies have shown

Figure 1: Control group.A scanning electron microscope showing a tissue of the liver of male rats in the control group. The hepatocytes clear and have one nucleus (N) or two nuclei. (X3000).

Figure 2: Control group.A scanning electron microscope showing the ultrastructure of the well-formed hepatocytes (Hc) and the plasma membrane (Pm) and spread in the cytoplasm, the rough endoplasmic reticulum (RER), the smooth endoplasmic reticulum (SER), mitochondria (M), and the nucleus clear (Nu). The hetero chromatin(He), (Eu) Euochromatinand (X6000).

Figure 3: Control group.A scanning electron microscope image showing the presence of the nucleus (N) and the distribution of chromatin around the nucleus (Eu). The coarse endoplasmic reticulum (RER) is also present regularly, as well as the smooth endoplasmic reticulum (SER) and spherical mitochondria (M). You clearly see the blood sinusoids (S) within which there are blood cells Red (RBC) (X8000).

the occurrence of hepatitis, high blood lipids and sugar in the blood plasma. In this study, rat depression was treated with a dose of 6 ml/ kg body weight for eight weeks. Body weight was observed through the gastric tube based on previous studies and doses were given without depriving rats from food or water represented by the natural person taking doses of the medication on the group of treated rats. The results showed liver cell damage and increase in Kupffer cell count, which was confirmed [4]. Antidepressants have

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Figure 4: Control group.A photocopy of the penetrating electron microscope, showing a hematopoietic sinus of the liver tissue, showing a clear hepatocytes grouping (Hc), with clear nuclei (N), showing the outer edge of the cells and in which the micro villi (Mv) overlooking the space (SD) and showing the hematopoietic (S) containing blood cells Red (RBC) and Kupffer cells (K). (X5000).

Figure 5: Control group.A scanning electron microscope image showing the precise structure of the hepatic cell, where the nuclei appear clear (N), the smooth endoplasmic reticulum (SER), and spherical mitochondria (M), and the Kupffer cells (K) (S) lie inside the blood sinusoids (S) and epithelial cells (E) appear. ((X4000).

Figure 6: Control group.A scanning electron microscope image showing the precise composition of the parts of the hepatocytes where the spherical or oval mitochondria (M) appear and within them are regular norms and a Golgi apparatus (GO) appears between the mitochondria (M) and the coarse endoplasmic reticulum (RER) that appears well formed surrounding the nucleus and lysosome (L). ((X10000).

Figure 7: Treatment Group.A photograph of the electron microscope in force in a seg-ment of the liver of male, in which the hepatocyte are clearly visible, showing the nucleus and the nucleus with a terminal (Nu) surrounded by the nuclear membrane (Nm) containing the nuclear poor (Np). (X6000).

positive effects on the liver in both male and female rats [5,6]. Therefore, this study aims to determine the effect of Olan-

zapine on the liver and its harmful effects.Olanzapine (6 ml/ kg body weight) was used in this study

[7,8]. As agreed with SW Woods, [9]. Blood samples were taken from rats to examine blood sugar and lipids. This is an indication of hepatitis [10]. It was observed in patients taking olanzapine (weight gain, fat disorder, insulin resistance and hypertension).

Blood sugar as the transcription reflects a lower glucose

metabolism rate. It is reported that olanzapine has a strong correlation with the emergence of new diabetes.

[11] Weight gain is one of the risk factors for diabetes. It was observed that when APDs were discontinued, plasma glucose was reduced [12,13].

[14,15] In animal models, anti-psychotic medications (APDs) have been shown to cause hyperthyroidism, leading to weight gain and high blood sugar [16].

[11] The group treated with Olanzapine:The histological study of the liver of male rats treated with

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Figure 8: Treatment Group.A photocopy of the transmission electron microscope that shows the precise structure of the liver tissue of male rats treated with olanzapine, in which the bile duct malformation (Bd) and the evident change in the spherical mitochondria (M) occur where deformation and degradation of internal mitochondria occurs as well as the appearance of the rough endoplasmic reticulum (RER) and the smooth endoplasmic reticulum. (SER) and the emergence of glycogen. (G) (X30000).

Figure 9: Treatment Group.A scanning electron microscope showing the ultra structure of the liver tissue of male rats treated with olanzapine. The space of disse (SD) space also shows the presence of lipid accumulation (Lp). And lysosome ( L) (X25000).

Figure 10: Treatment Group.A scanning electron microscope showing the precise structure of the liver tissue of male rats treated with olanzapine showing the nucleus (N) and the hetero-chromatin (He) close to the nuclear envelope and Euo chromatin (Eu) around the nucleus and the appearance of medullary bodies (Mf ) and lysosome (L) (x25000).

Figure 11: Treatment Group.A photograph of the electron microscope in force in a section of the liver of male rats treated with olanzapine. It shows acute deformation in the shape of the nucleus (N) and distribution of chromatin and shows the nucleus (Nu) and the decomposi-tion of the cytoplasm (Cd) as well as degeneration of lysosome (L) and deformation of the bile duct (Bc) and deformation of the nucleus of Kupffer cells. (K) We also find the smooth endoplasmic reticulum (SER) and the abundance of glycogen (G (x15000).

olanzapine showed several different changes appearing in the composition of the liver cells due to the appearance of many cell necrosis, atrophy of nuclei and severe tissue abnormalities and widening of the sinuses, fluid runoff, vas-cular congestion, blood stasis, and increase of Kupffer cells was seen as a result of the severity of inflammation, cellular degradation and nuclei deny. Deformity and congestion of the portal artery are observed, the multiplication of the bile ducts

and the severe damage to the liver cells; there was a sharp expansion of the hepatic artery, endothelial cell enlargement and liver cell decomposition. Central hepatic vein fibrosis has also been severely seen as a result of inflammation and blood stasis within it, hematuria, abnormal proliferation of bile ducts, hepatic artery enlargement, endothelial separa-tion, inflammatory cell appearance, and some fat drops as evidenced [17]. The group treated with olanzapine showed

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Figure 12: Treatment Group.A scanning electron microscope of a section in the liver of male rats treated with olanzapine showing a clear degradation of mitochondrial norms (M) and increased deformation of SD space inertia (it) ito-cell morphology and collagen fibers (Cf) inside the lumen (Mf ) and lysosomal bodies (L) Acute deformation of the spherical and oval mitochondria (M) frequent hematopoietic sinuses (S) and increased multiplication of the bile ducts. (Bd) (X8000).

Figure 13: Treatment Group.A photocopy of the electron microscope in force in a seg-ment of the liver of male rats treated with olanzapine. It shows pathological changes in the hepatocyte, where it shows the decomposition of the nuclear membrane (Nm), the increase in heterochromatin (He) and (Eu) Euochromatin and nuclear decomposition and deformation, where the nucleus (N) and acute deformation in Golgi apparatus (Go), internal norms analysis, acute deformations in mitochondria (M) and glycogen prevalence in the cytoplasm (G). (X15000).

Figure 14: Treatment Group.A photograph of the electron microscope in liver of the male rats treated with olanzapine. It shows acute deformation in the bile ducts (Bc) and the analysis of the nucleus of the Kupffer cell (K) and lysosomes. (L) (x30000).

Figure 15: Treatment Group.A photograph of the electron microscope in the liver of male rats treated with olanzapine, showing bile duct malformations (Bc), Golgiaoparatus (Go) degradation, Cytoplasmic degnaration (Cd) and mitochondria (M), presence of medullary (Mf) and lysosomes (L). (X25000).

fibrosis and seborrhea hepatitis, as large drops of fat were observed in the areas surrounding the nucleus and increased smooth network, as well as a large number of myelin fibers. He showed a marked increase in the level of cholesterol in the blood throughout the treatment period, and the results

were significantly higher after the third week (44.69%) and this consistent with the results [18]. The deformation of the portal vein, the macrophage cell multiplicity, the severity of inflammation, enlarged nucleus, and hematogenesis are strongly observed within the central vein. Olanzapine causes pathological changes in the liver. A significant increase in body weight was observed throughout the treatment period, after the first week (55.87%). This is consistent with [19]. This is also consistent with the increase in body weight in the olanzapine group with a study [20]. There was a significant increase in the level of cholesterol throughout the treatment period, and the results recorded the highest significant increase after the

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Figure 16: Treatment Group.A photocopy of the electron microscope that permits a sec-tion in the liver of the male rats of the group treated with olanzapine. Acute malformation occurs in the hepatic cell and you see the myeloid forms (Mf) and collagen fibers (Cf) that work on cirrhosis as well as lysosomal (L) and increase of fat drops (Lp) and bodies. Laminar (Lb) in dice-space (SD) and degeneration micro villi (Mv). (X20000)).

Figure 17: Treatment Group.A photocopy of the electron microscope in a section of the liver of male rats of the showing blood sinusoids (S) and fat lipids (Lp) in the cytoplasm and space of disse (SD) and ito-fat (It) cells that store fat and blood sinusoids (S). (X5000).

Figure 18: Treatment Group.A photograph of the electron microscope in force in a section of the liver of male rats showing the well-formed nucleus (N) with two nuclei (Nu) and nuclear holes (Np) and fatty acids (Lp) and showing Kupffer cell (K) cells and sinuses Blood (S) Golgioparatas (Go) device and coarse endoplasmic reticulum (RER) (X6000).

Figure 19: Treatment Group.A photograph of the electron microscope in force in a liver of male rats (M) mitochondrial forms, analysis of mitochondrial norms (inner layer), abundance of smooth endoplasmic reticulum (SER), and bile canaliculus (Bc), and a space of disse appears. (SD) (X8000).

third week (44.69%), which corresponds to [21].As [22] mentioned, olanzapine has been positively asso-

ciated with weight gain, cholesterol and sugar. There was a clear increase in the expansion of the blood pockets and the increase in the Kupffer cells, the severity of inflammation and deformation in the form of irregular nuclei and chromatin, deformation of mitochondrial forms, hypo-density, dimin-ishing numbers and the appearance of gaps within them, internal dissolution, degradation of the rough endoplasmic reticulum and bile duct deformation. Increased bile duct multiplication from the severity of inflammation, increased

fat, increased myelin fibers, and the emergence of ITO cells to store fat, consistent with [17,22].

Pathological changes also show the shape of endothelial cells, Kupffer cells, nucleus irregularities, increased homoge-neous chromatin masses, decreased electron density, het-erogeneous chromatin, nucleation and nuclear abnormality, which reduce functional efficiency and deformation of the Golgiapparatus [23]. Cellular swelling and membrane damage have been detected. Programmed cell death occurs while the cell membrane remains intact.

Chronic olanzapine treatment results in a low-grade inflam-

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Figure 20: Treatment Group.A photograph of the electron microscope in a section of the liver of male rats showing blood stagnation (RBC) and Kupffer cells (K) inside the sinuses Blood (S) (X12000).

Figure 21: Treatment Group.A photogrammetry of the electron microscope in force in a male liver. Rats analyzing and altering the shape of the nucleus (N), chromatin distribution, and decomposition of mitochondria (M) and glycogen assemblies (G) in the cytoplasm and coarse endoplasmic reticulum (RER). (X50000).

Figure 22: Treatment Group.Photographic electron microscopy of in the liver of male rats showing the nucleus, including chromatin and nuclear poor (Np) and the presence of coarse endoplasmic reticulum (RER) and glycogen concentrations (G) X25000).

matory condition, which is likely to start in adipose tissue.Such an inflammatory condition is known to be associated

with an increased risk of insulin resistance and cardiovascular disease. This inflammatory syndrome caused by antipsychotics may participate in the inflammatory syndrome that is often observed in schizophrenia patients. The strong and selective effect of olanzapine on the expression of TNFα may open new therapeutic opportunities for the prevention of meta-bolic abnormalities in olanzapine [24]. The cytotoxic effect of olanzapine on newly isolated rat liver cells was assessed. Cytotoxicity of olanzapine in liver cells mediated by excessive production of reactive oxygen species (ROS), possible mito-chondrial collapse, lysosome membrane degradation, GSH

depletion, and lipid peroxide preceded by cell degradation. Current results have shown that CYP450 caused olanzapine-induced oxidative stress and cellular toxicity mechanism. It was concluded that hepatotoxicity of olanzapine was associated with both mitochondria and increased lysosome after the onset of oxidative stress in liver cells. Increased mitochondrial degradation and frequent presence of smooth endoplasmic reticulum due to excess fat.

Conclusions1. Olanzapine antidepressants, which are used to treat

depression and psychosis, have harmful effects on the liver and weight gain.

2. Not to take too much antidepressants because they harm the liver.

3. Antidepressants increase blood sugar.

Competing interestsThe authors declare that they have no competing interests.

AcknowledgementI thank the University of Jeddah for providing the opportunity to conduct research in the Laboratories, Material support and help in the Dissemination of research as well as a continuous thanks to the scientific journal of histology and histopathology and thanks to King Faisal University in Dammam for the use and work of the electronic microscope sectors.

Publication historyEditor: Khin Thway, The Royal Marsden Hospital, UK.Received: 04-Feb-2020 Final Revised: 16-Mar-2020Accepted: 25-Apr-2020 Published: 21-May-2020

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Citation:Batarfi NM. Ultrastructure and Pathology Study of the Effect of an Antidepressant (Olanzapine) on the Health of Mitochondria in liver of male Albino Rat. J Histol Histopathol. 2020; 7:3. http://dx.doi.org/10.7243/2055-091X-7-3