Foods and Raw Materials Foods and Raw Materials Foods and Raw Materials 2308-4057 2310-9599 95025 10.21603/2308-4057-2026-1-654 Research Article Research Article Research Article Fiber supplements from agro-industrial waste: Effect on valproic acid hepatotoxicity in rats Fiber supplements from agro-industrial waste: Effect on valproic acid hepatotoxicity in rats https://orcid.org/0000-0001-9989-7978 Ramirez Maria Rosana Ramirez Maria Rosana mr.ramirez@conicet.gov.ar https://orcid.org/0000-0003-2523-6530 Manuale Debora Manuale Debora https://orcid.org/0000-0001-8874-6242 Yori Juan C. Yori Juan C. National Scientific and Technical Research Council Buenos Aires Аргентина National Scientific and Technical Research Council Buenos Aires Argentina National Scientific and Technical Research Council Buenos Aires Аргентина National Scientific and Technical Research Council Buenos Aires Argentina National Scientific and Technical Research Council Buenos Aires Аргентина National Scientific and Technical Research Council Buenos Aires Argentina 14 02 2025 14 02 2025 14 1 61 70 27 03 2024 04 06 2024 https://jfrm.ru/en/issues/23173/23286/

The agro-industrial sector is one of the biggest organic waste producers. Instead of being discarded into the environment, fruit and vegetable waste could be processed to obtain added value. This article introduces pomace fiber powder made from agroindustrial waste of fruits and vegetables. Its protective potential against hepatotoxicity induced by valproic acid was studied in Wistar rats, both as preventive and curative treatments. In the preventive test, valproic acid (250 mg/kg/day) was administered orally together with the pomace fiber powder (0.3 and 0.15 mg/kg/day) for 14 days. In the curative test, the rats received valproic acid for 14 days, followed by pomace fiber powder another 14 days, at the same amounts. Physicochemical analysis revealed that the experimental pomace fiber powder contained 15.2 ± 0.5% and 22.0 ± 1.2% of insoluble and soluble dietary fiber, respectively. This ratio made it possible to classify the new supplement as functional. The rats administered with valproic acid gained body weight and demonstrated a significant increase in serum enzyme activities, alanine aminotransferase, and alkaline phosphatase (p < 0.05). These results were confirmed by histopathological examination. In both preventive and curative treatments, the supplementation normalized body weight, improved liver biomarkers, and attenuated the hepatic injury induced in rats by valproic acid. The new pomace fiber powder made of agro-industrial waste proved to be an effective raw material that attenuates the side effects associated with prolonged valproic acid administration.

The agro-industrial sector is one of the biggest organic waste producers. Instead of being discarded into the environment, fruit and vegetable waste could be processed to obtain added value. This article introduces pomace fiber powder made from agroindustrial waste of fruits and vegetables. Its protective potential against hepatotoxicity induced by valproic acid was studied in Wistar rats, both as preventive and curative treatments. In the preventive test, valproic acid (250 mg/kg/day) was administered orally together with the pomace fiber powder (0.3 and 0.15 mg/kg/day) for 14 days. In the curative test, the rats received valproic acid for 14 days, followed by pomace fiber powder another 14 days, at the same amounts. Physicochemical analysis revealed that the experimental pomace fiber powder contained 15.2 ± 0.5% and 22.0 ± 1.2% of insoluble and soluble dietary fiber, respectively. This ratio made it possible to classify the new supplement as functional. The rats administered with valproic acid gained body weight and demonstrated a significant increase in serum enzyme activities, alanine aminotransferase, and alkaline phosphatase (p < 0.05). These results were confirmed by histopathological examination. In both preventive and curative treatments, the supplementation normalized body weight, improved liver biomarkers, and attenuated the hepatic injury induced in rats by valproic acid. The new pomace fiber powder made of agro-industrial waste proved to be an effective raw material that attenuates the side effects associated with prolonged valproic acid administration.

 Food waste waste minimization pomace sustainable production bioeconomy fiber hepatotoxicity Food waste waste minimization pomace sustainable production bioeconomy fiber hepatotoxicity This work was supported by the National Agency for the Promotion of Research, Technological Development and Innovation (ANPCyT), PICT-2020-SERIE A-03055, and the National Scientific Research Council of the Argentina government (CONICET) , PIP Project N° 11220200103171CO and PIP No. 11220200100054. This work was supported by the National Agency for the Promotion of Research, Technological Development and Innovation (ANPCyT), PICT-2020-SERIE A-03055, and the National Scientific Research Council of the Argentina government (CONICET) , PIP Project N° 11220200103171CO and PIP No. 11220200100054.

Clementz A, Torresi PA, Molli JS, Cardell D, Mammarella E, Yori JC. Novel method for valorization of by-products from carrot discards. LWT. 2019;100:374–380. https://doi.org/10.1016/j.lwt.2018.10.085 Clementz A, Torresi PA, Molli JS, Cardell D, Mammarella E, Yori JC. Novel method for valorization of by-products from carrot discards. LWT. 2019;100:374–380. https://doi.org/10.1016/j.lwt.2018.10.085 Lucarini M, Durazzo A, Bernini R, Campo M, Vita C, Souto EB, et al. Fruit Wastes as a Valuable Source of Value-Added Compounds: A Collaborative Perspective. Molecules. 2021;26(21):6338. https://doi.org/10.3390/molecules26216338 Lucarini M, Durazzo A, Bernini R, Campo M, Vita C, Souto EB, et al. Fruit Wastes as a Valuable Source of Value-Added Compounds: A Collaborative Perspective. Molecules. 2021;26(21):6338. https://doi.org/10.3390/molecules26216338 Ramirez MR, Manuale D, Yori JC. Assessment of effectiveness of oral supplementation of isolated fiber of carrot on metabolic parameters in mature rats. Food Science and Human Wellness. 2023;12(6):2022–2028. https://doi.org/10.1016/j.fshw.2023.03.016 Ramirez MR, Manuale D, Yori JC. Assessment of effectiveness of oral supplementation of isolated fiber of carrot on metabolic parameters in mature rats. Food Science and Human Wellness. 2023;12(6):2022–2028. https://doi.org/10.1016/j.fshw.2023.03.016 Ramirez MR, Rintoul I, Leiva M, Molli JS, Yori JC. Oral supplementation of Ilex paraguariensis extract and eggshell membrane exhibit beneficial effects on the skin of mature male rats. Journal of Pharmacy and Pharmacognosy Research. 2023;11(2):216–228. https://doi.org/10.56499/jppres22.1509_11.2.216 Ramirez MR, Rintoul I, Leiva M, Molli JS, Yori JC. Oral supplementation of Ilex paraguariensis extract and eggshell membrane exhibit beneficial effects on the skin of mature male rats. Journal of Pharmacy and Pharmacognosy Research. 2023;11(2):216–228. https://doi.org/10.56499/jppres22.1509_11.2.216 Okpoghono J, Ukperegbulem JK, Igue UB. Anti-lipidemic and protein restoration potential of Monodora myristica (Gaertn.) in rats fed with cassava containing crude oil. Foods and Raw Materials. 2024;12(2):249–255. https://doi.org/10.21603/2308-4057-2024-2-602 Okpoghono J, Ukperegbulem JK, Igue UB. Anti-lipidemic and protein restoration potential of Monodora myristica (Gaertn.) in rats fed with cassava containing crude oil. Foods and Raw Materials. 2024;12(2):249–255. https://doi.org/10.21603/2308-4057-2024-2-602 Pouwels S, Sakran N, Graham Y, Leal A, Pintar T, Yang W, et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocrine Disorders. 2022;22(1):63. https://doi.org/10.1186/s12902-022-00980-1 Pouwels S, Sakran N, Graham Y, Leal A, Pintar T, Yang W, et al. Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss. BMC Endocrine Disorders. 2022;22(1):63. https://doi.org/10.1186/s12902-022-00980-1 Walter SR, Day RO, Gallego B, Westbrook JI. The impact of serious adverse drug reactions: a population-based study of a decade of hospital admissions in New South Wales, Australia. British Journal of Clinical Pharmacology. 2017;83:416–426. https://doi.org/10.1111/bcp.13124 Walter SR, Day RO, Gallego B, Westbrook JI. The impact of serious adverse drug reactions: a population-based study of a decade of hospital admissions in New South Wales, Australia. British Journal of Clinical Pharmacology. 2017;83:416–426. https://doi.org/10.1111/bcp.13124 Shnayder NA, Grechkina VV, Khasanova AK, Bochanova EN, Dontceva EA, Petrova MM, et al. Therapeutic and Toxic Effects of Valproic Acid Metabolites. Metabolites. 2023;13(1):134. https://doi.org/10.3390/metabo13010134 Shnayder NA, Grechkina VV, Khasanova AK, Bochanova EN, Dontceva EA, Petrova MM, et al. Therapeutic and Toxic Effects of Valproic Acid Metabolites. Metabolites. 2023;13(1):134. https://doi.org/10.3390/metabo13010134 Pirozzi C, Lama A, Annunziata C, Cavaliere G, De Caro C, Citraro R, et al. Butyrate prevents valproate-induced liver injury: In vitro and in vivo evidence. FASEB Journal. 2020;34(1):676–690. https://doi.org/10.1096/fj.201900927RR Pirozzi C, Lama A, Annunziata C, Cavaliere G, De Caro C, Citraro R, et al. Butyrate prevents valproate-induced liver injury: In vitro and in vivo evidence. FASEB Journal. 2020;34(1):676–690. https://doi.org/10.1096/fj.201900927RR Abdelkader NF, Elyamany M, Gad AM, Assaf N, Fawzy HM, Elesawy WH. Ellagic acid attenuates liver toxicity induced by valproic acid in rats. Journal of Pharmacological Science. 2020;143(1):23–29. https://doi.org/10.1016/j.jphs.2020.01.007 Abdelkader NF, Elyamany M, Gad AM, Assaf N, Fawzy HM, Elesawy WH. Ellagic acid attenuates liver toxicity induced by valproic acid in rats. Journal of Pharmacological Science. 2020;143(1):23–29. https://doi.org/10.1016/j.jphs.2020.01.007 Abdel-Dayem MA, Elmarakby AA, Abdel-Aziz AA, Pye C, Said SA, El-Mowafy AM. Valproate-induced liver injury: Modulation by the omega-3 fatty acid DHA proposes a novel anticonvulsant regimen. Drugs in R and D. 2014;14(2):85–94. https://doi.org/10.1007/s40268-014-0042-z Abdel-Dayem MA, Elmarakby AA, Abdel-Aziz AA, Pye C, Said SA, El-Mowafy AM. Valproate-induced liver injury: Modulation by the omega-3 fatty acid DHA proposes a novel anticonvulsant regimen. Drugs in R and D. 2014;14(2):85–94. https://doi.org/10.1007/s40268-014-0042-z Liu X, Yang W, Petrick JL, Liao LM, Wang W, He N, et al. Higher intake of whole grains and dietary fiber are associated with lower risk of liver cancer and chronic liver disease mortality. Nature Communication. 2021;12:6388. https://doi.org/10.1038/s41467-021-26448-9 Liu X, Yang W, Petrick JL, Liao LM, Wang W, He N, et al. Higher intake of whole grains and dietary fiber are associated with lower risk of liver cancer and chronic liver disease mortality. Nature Communication. 2021;12:6388. https://doi.org/10.1038/s41467-021-26448-9 Zhao H, Yang A, Mao L, Quan Y, Cui J, Sun Y. Association Between Dietary Fiber Intake and Non-alcoholic Fatty Liver Disease in Adults. Frontiers in Nutrition. 2020;7:593735. https://doi.org/10.3389/fnut.2020.593735 Zhao H, Yang A, Mao L, Quan Y, Cui J, Sun Y. Association Between Dietary Fiber Intake and Non-alcoholic Fatty Liver Disease in Adults. Frontiers in Nutrition. 2020;7:593735. https://doi.org/10.3389/fnut.2020.593735 Official methods of analysis AOAC, 17th ed. Gaithersburg, MD, USA. The Association of Official Analytical Chemists; 2000. Official methods of analysis AOAC, 17th ed. Gaithersburg, MD, USA. The Association of Official Analytical Chemists; 2000. Parra-Orobio BA, Rotavisky-Sinisterra MP, Pérez-Vidal A, Marmollejo-Revellon LF, Torres-Lozada P. Physicochemical, microbiological characterization and phytotoxicity of digestates produced on single-stage and two-stage anaerobic digestion of food waste. Sustainable Environment Research. 2021;31:11. https://doi.org/10.1186/s42834-021-00085-9 Parra-Orobio BA, Rotavisky-Sinisterra MP, Pérez-Vidal A, Marmollejo-Revellon LF, Torres-Lozada P. Physicochemical, microbiological characterization and phytotoxicity of digestates produced on single-stage and two-stage anaerobic digestion of food waste. Sustainable Environment Research. 2021;31:11. https://doi.org/10.1186/s42834-021-00085-9 Issy AM, Lanchote VL, de Carvalho D, Silva HC. Lack of kinetic interaction between valproic acid and citrus pectin. Therapeutic Drug Monitoring. 1997;19(5):516–520. https://doi.org/10.1097/00007691-199710000-00005 Issy AM, Lanchote VL, de Carvalho D, Silva HC. Lack of kinetic interaction between valproic acid and citrus pectin. Therapeutic Drug Monitoring. 1997;19(5):516–520. https://doi.org/10.1097/00007691-199710000-00005 Ramirez MR, Mohamad L, Alarcon-Segovia LC, Rintoul I. Effect of Processing on the Nutritional Quality of Ilex paraguariensis. Applied Sciences. 2022;12(5):2487. https://doi.org/10.3390/app12052487 Ramirez MR, Mohamad L, Alarcon-Segovia LC, Rintoul I. Effect of Processing on the Nutritional Quality of Ilex paraguariensis. Applied Sciences. 2022;12(5):2487. https://doi.org/10.3390/app12052487 Cantero I, Abete I, Monreal JI, Martinez JA, Zulet MA. Fruit Fiber Consumption Specifically Improves Liver Health Status in Obese Subjects under Energy Restriction. Nutrients. 2017;9(7):667. https://doi.org/10.3390/nu9070667 Cantero I, Abete I, Monreal JI, Martinez JA, Zulet MA. Fruit Fiber Consumption Specifically Improves Liver Health Status in Obese Subjects under Energy Restriction. Nutrients. 2017;9(7):667. https://doi.org/10.3390/nu9070667 Caroline W, Martin H, Katarzyna L, Robert W, Norbert S, Jürgen M. Potential effects of reduced red meat compared with increased fiber intake on glucose metabolism and liver fat content: a randomized and controlled dietary intervention study. The American Journal of Clinical Nutrition. 2019;109(2):288–296. https://doi.org/10.1093/ajcn/nqy307 Caroline W, Martin H, Katarzyna L, Robert W, Norbert S, Jürgen M. Potential effects of reduced red meat compared with increased fiber intake on glucose metabolism and liver fat content: a randomized and controlled dietary intervention study. The American Journal of Clinical Nutrition. 2019;109(2):288–296. https://doi.org/10.1093/ajcn/nqy307 Xu S, Chen Y, Ma Y, Liu T, Zhao M, Wang Z, et al. Lipidomic Profiling Reveals Disruption of Lipid Metabolism in Valproic Acid-Induced Hepatotoxicity. Frontiers in Pharmacology. 2019;10:819. https://doi.org/10.3389/fphar.2019.00819 Xu S, Chen Y, Ma Y, Liu T, Zhao M, Wang Z, et al. Lipidomic Profiling Reveals Disruption of Lipid Metabolism in Valproic Acid-Induced Hepatotoxicity. Frontiers in Pharmacology. 2019;10:819. https://doi.org/10.3389/fphar.2019.00819 Hannon BA, Thompson SV, Edwards CG, Skinner SK, Niemiro GM, Burd NA, et al. Dietary Fiber Is Independently Related to Blood Triglycerides Among Adults with Overweight and Obesity. Current Development in Nutrition. 2019;3(2):nzy094. https://doi.org/10.1093/cdn/nzy094 Hannon BA, Thompson SV, Edwards CG, Skinner SK, Niemiro GM, Burd NA, et al. Dietary Fiber Is Independently Related to Blood Triglycerides Among Adults with Overweight and Obesity. Current Development in Nutrition. 2019;3(2):nzy094. https://doi.org/10.1093/cdn/nzy094 He J, Zhang P, Shen L, Niu L, Tan Y, Chen L, et al. Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism. International Journal of Molecular Sciences. 2020;21(17):6356. https://doi.org/10.3390/ijms21176356 He J, Zhang P, Shen L, Niu L, Tan Y, Chen L, et al. Short-Chain Fatty Acids and Their Association with Signalling Pathways in Inflammation, Glucose and Lipid Metabolism. International Journal of Molecular Sciences. 2020;21(17):6356. https://doi.org/10.3390/ijms21176356 Chen J, Huang Y, Xie H, Bai H, Lin G, Dong Y, et al. Impact of a low-carbohydrate and high-fiber diet on nonalcoholic fatty liver disease. Asia Pacific Journal of Clinical Nutrition. 2020;29(3):483–490. https://doi.org/10.6133/apjcn.202009_29(3).0006 Chen J, Huang Y, Xie H, Bai H, Lin G, Dong Y, et al. Impact of a low-carbohydrate and high-fiber diet on nonalcoholic fatty liver disease. Asia Pacific Journal of Clinical Nutrition. 2020;29(3):483–490. https://doi.org/10.6133/apjcn.202009_29(3).0006 Pérez-Montes de Oca A, Julián MT, Ramos A, Puig-Domingo M, Alonso N. Microbiota, Fiber, and NAFLD: Is There Any Connection? Nutrients. 2020;12(10):3100. https://doi.org/10.3390/nu12103100 Pérez-Montes de Oca A, Julián MT, Ramos A, Puig-Domingo M, Alonso N. Microbiota, Fiber, and NAFLD: Is There Any Connection? Nutrients. 2020;12(10):3100. https://doi.org/10.3390/nu12103100 Maciejewska-Markiewicz D, Drozd A, Palma J, Ryterska K, Hawryłkowicz V, Zał˛eska P, et al. Fatty Acids and Eicosanoids Change during High-Fiber Diet in NAFLD Patients—Randomized Control Trials (RCT). Nutrients. 2022;14(20):4310. https://doi.org/10.3390/nu14204310 Maciejewska-Markiewicz D, Drozd A, Palma J, Ryterska K, Hawryłkowicz V, Zał˛eska P, et al. Fatty Acids and Eicosanoids Change during High-Fiber Diet in NAFLD Patients—Randomized Control Trials (RCT). Nutrients. 2022;14(20):4310. https://doi.org/10.3390/nu14204310 Jahromi SR, Togha M, Fesharaki SH, Najafi M, Moghadam NB, Kheradmand JA, et al. Gastrointestinal adverse effects of antiepileptic drugs in intractable epileptic patients. Seizure. 2011;20:343–346. https://doi.org/10.1016/j.seizure.2010.12.011 Jahromi SR, Togha M, Fesharaki SH, Najafi M, Moghadam NB, Kheradmand JA, et al. Gastrointestinal adverse effects of antiepileptic drugs in intractable epileptic patients. Seizure. 2011;20:343–346. https://doi.org/10.1016/j.seizure.2010.12.011