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Exploring the Multimodal Role of Yucca schidigera Extract in Protection against Chronic Ammonia Exposure Targeting:

Growth, Metabolic, Stress and Inflammatory Responses in Nile Tilapia (Oreochromis niloticus L.)

By: Zizy I. Elbialy, Abdallah S. Salah, Ahmed Elsheshtawy, Merna Rizk, Muyassar H. Abualreesh, Mohamed M. Abdel-Daim, Shimaa M. R. Salem, Ahmad El Askary and Doaa H. Assar.

ABSTRACT. Despite trials for its control, ammonia remains one of the most environmental toxicant for aquatic species. In this study, we explored the modulatory effect and potential mechanism by which Yucca schidigera extract (YSE) can ameliorate ammonia intoxication-induced adverse effects on tilapia health and metabolism. YSE supplementation succeeded in improving water quality, markedly alleviated chronic ammonia-induced adverse impacts on fish growth while reducing the feed conversion ratio (FCR) via improvements in food intake, elevation of hepatic insulin-like growth factor (ILGF-1) and suppression of myostatin (MSTN) expression levels with the restoration of lipid reserves and the activation of lipogenic potential in adipose tissue as demonstrated by changes in the circulating metabolite levels. This suggests that YSE supplementation exerted an ameliorative role against chronic ammonia-induced oxidative stress and toxic effects due to its free radical-scavenging potential, potent antioxidant activities and anti-inflammatory effects.

The intensification of aquaculture causes water pollution, which is consistently related to increased levels of ammonia, and represents about 70% of nitrogenous fish wastes. Decomposed un-eaten feed in water favors ammonia formation, and thus subjects fish to stress risk. Ammonia induces oxidative stress via the overproduction of ROS (reactive oxygen species), which deteriorates important biomolecules, such as DNA, proteins and lipids, and initiates a cascade of events that causes impairment of cellular functions.

Yucca schidigera is a medicinal herb which represents an important future ecofriendly supplement in livestock production. Numerous studies documented that Yucca schidigera extract (YSE) has the ability to regulate energy metabolism and hormonal activity in animals.

Nile tilapia (Oreochromis niloticus L.) is an important cultured aquaculture species throughout the world that could be used as a suitable model for studying nutrition and metabolism not only because of its rapid growth and high resistance to diseases and toxic stress, but also due to the availability of its whole genomic information. The present investigation aimed to declare YSE modulatory effect (s) against chronic ammonia intoxication in Nile Tilapia (Oreochromis niloticus).

Experimental Design, fish diet and water quality

A total of 120 healthy male monosex Nile tilapia (Oreochromis niloticus) were collected from a private farm, acclimated for two weeks, and then divided into four groups. The first group kept as a normal control group, the second group supplied with YSE in water at a dose of 8 mg/L water every two days, the third group exposed to ammonia from the beginning of the experiment for four weeks, and the fourth group was supplied with YSE and exposed to ammonia for four weeks.

Different water parameters were measured on a daily basis throughout the experiment’s duration, including dissolved oxygen (DO), ammonia, water temperature, and pH, in all experimental groups.

Blood Sampling, evaluation of Lipid Peroxidation and Antioxidant Enzymes

After four weeks, blood samples were collected from fish in a random order from the caudal vein and divided into two parts. for biochemical measurements of transaminases (ALT and AST), LDH, amylase, lipase, TC, TG, HDL-C, total proteins, albumin, BUN.

A piece of liver was subjected to biochemical determination of malondialdehyde (MDA) content, and glutathione peroxidase (GPx). Superoxide dismutase (SOD) was evaluated and reduced glutathione (GSH).

Histopathology Study, total RNA Extraction, cDNA Synthesis and Quantitative PCR Assay Sections from liver, spleen, brain and gills were dehydrated using ascending concentrations of ethanol (70–100%), cleared in xylene, and embedded in paraffin wax, cut on a microtome, stained with hematoxylin and eosin (H&E) and examined with a light microscope.

To evaluate gene expression levels, liver, adipose, muscle and brain tissues (3 fish/replicate) were collected. Gene expression analysis was performed in the mic-PCR Real-time PCR system (Bio-molecular systems) using the SensiFast SYBR No-Rox kit (Bioline) using Nile tilapia genespecific primers with 16s rRNA as the housekeeping gene.


YSE supplementation significantly reduced (p < 0.05) pH, TAN and UIA levels compared to the fish group exposed to high ammonia levels. Moreover, compared to the control group, fish exposed only to high ammonia level showed significantly lowered FBW (final body weight), BWG (body weight gain), and SGR (specific growth rate), and higher FCR (feed conversion ratio). Conversely, supplying YSE to ammonia-intoxicated fish successfully enhanced FBW, BWG, and SGR and significantly lowered FCR in comparison to the fish group exposed only to high ammonia levels.

YSE administration to ammoniaintoxicated fish restored the values of the stress leukogram to normal reference levels compared to the second fish group, which was intoxicated by high ammonia levels, where no changes occurred. YSE resulted in an effective improvement according to the measurement of ammonia- altered hepatorenal injury markers.

The findings of ammonia-intoxicated fish additionally supplied with YSE were opposed to the findings for the ammonia-intoxicated group, in which there was an inhibition of hepatic MDA content and an enhancement of SOD, GPx enzyme activities and GSH levels. Ammonia intoxication induced marked degenerative and necrotic changes within the hepatopancreas (P) with a moderate degree of hepatic vacuolation. However, YSE treatment markedly improved pathological changes in the hepatopancreas that were induced by high ammonia levels.

On the other hand, YSE treatment to ammonia-intoxicated fish had improved the MMC However, the administration of YSE to ammoniaintoxicated fish resulted in tiny foci of malacia with a marked decrease in gliosis. Additionally, an elevated ammonia level induced severe loss of secondary lamellae with marked infiltration of inflammatory cells, while YSE treatment resulted in a marked decrease in the adhesion between the secondary lamellae.

The second fish group, which was intoxicated by ammonia, had reduced levels of both brain NPY and hepatic IGF1. The fish group supplied with YSE and intoxicated with ammonia (3rd group) exhibited higher expression levels of brain NPY, and hepatic IGF1, with a decreased expression of liver MSTN compared with the chronically intoxicated ammonia group.

Compared to the control group, the ammonia- intoxicated group exhibited reduced expression levels of glycolytic gene PK and adipose tissue lipogenesis encoding of the FAS gene, as well as elevated gluconeogenesis genes G6pase and PEPCK and enhanced adipose tissue lipolysis regulating the LPL gene the groups supplied with YSE, either with ammonia intoxication or without, experienced down regulation of the hepatic IL1B, TNFα and HSP70 gene expression levels compared to the ammonia- intoxicatedonly fish group after two and four weeks.


High ammonia level was harmful to Nile tilapia through the induction of oxidative stress via an elevated hepatic MDA content with depletion in the measured level of hepatic antioxidant defense markers. Digestive enzyme activities are good indicators of digestive capacity and precisely reflected the nutritional status of fish, and they are also highly sensitive to ROS.

We found that the growth-suppressing effects of chronic ammonia exposure may have resulted from the downregulation of brain NPY and hepatic ILGF-1 and the elevation of myostatin (MYSN) expression levels, in addition to the depletion of lipid reserves through the enhancement of adipose tissue lipolysis and the diminution of the adipo-lipogenic potential. fish intoxicated with ammonia compared with control group revealed reduced NPYa expression with elevated serum glucose levels and enhanced gluconeogenesis and lipolytic activity of LPL, suggesting that chronic ammonia stress could indirectly inhibit food intake through the hyperglycemic and lipolytic effects.

More specifically, we demonstrated here for the first time that YSE supplementation counteracted the suppressive effects of high ammonia levels on Nile tilapia growth at the molecular level through enhancement of brain NPYa, hepatic ILGF1 and inhibition of hepatic MSTN expression levels.

The hemato-biochemical indices reflect hepatic, renal and immune functions, as well as lipid and protein metabolism, in the blood of the organisms. Therefore, the general physiological and health condition of fish reared under stressful conditions or specifically supplied with modulatory agent can be well characterized. In this work, we challenged fish with ammonia level whose leukogram picture was indicative of stress. Interestingly, YSE supplementation for ammonia-intoxicated fish succeeded in producing a decline in the hepatic expression levels of TNF-α and IL-1Ɓ and a stress alteration in HSP70.

In the current work, ammonia intoxication was observed to lower the serum total proteins and albumin concentrations compared to the control fish group, which indicates the severe impairment of the tilapia immune system. However, high ammonia-stressed tilapia supplied with YSE demonstrated enhanced TP and albumin concentrations, reflecting the impact of YSE in regulating the nutrient metabolism of tilapia reared under either optimal or stressful conditions.

In this study, we found that ammonia-intoxicated fish showed a reduced adipose tissue FAS expression level and enhanced LPL expression level compared to the control fish group. During chronic stress, cortisol influences the liver physiology of fish by modulating the carbohydrate- and lipid-related metabolism.

Our data reinforced the hypothesis that the absence of a concomitant increase in hepatic glycolysis and the stimulation of gluconeogenesis in the liver may contribute to the establishment of elevated blood glucose levels.


Our results provided a novel perspective on the multiple interacting mechanisms through which YSE may exert its protective role against chronic ammonia toxicity. These results affirmed the growth-enhancing effects of YSE via the sustained enhancement of food intake, the elevation of IGF-1, the suppression of hepatic and brain MTSN expression levels, and the restoration of carbohydrate and lipid reserves, mediated through alterations in the levels of circulating metabolites.

Our results indicated that Yucca schidigera extract alleviated the adverse impacts induced by ammonia intoxication through its ability to scavenge free radicals, potent antioxidant activities and anti-inflammatory properties. The results of this study suggested that YSE supplementation was clearly beneficial for both health and growth in Nile tilapia, and that YSE could be used as a functional water supplement in aquaculture.

This informative version of the original article is sponsored by:

This is a summarized version developed by the editorial team of Aquaculture Magazine based on the review article titled “Exploring the Multimodal Role of Yucca schidigera Extract in Protection against Chronic Ammonia Exposure Targeting: Growth, Metabolic, Stress and Inflammatory Responses in Nile Tilapia (Oreochromis niloticus L.)” developed by: Zizy I. Elbialy, Abdallah S. Salah, Ahmed Elsheshtawy, Merna Rizk, Muyassar H. Abualreesh, Mohamed M. Abdel-Daim, Shimaa M. R. Salem, Ahmad El Askary and Doaa H. Assar. The original article was published on July, 2021, through the Animals Journal of MDPI under the use of a creative commons open access license. The full version can be accessed freely online through this link https://www.mdpi. com/2076-2615/11/7/2072.

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