Common Medicinal Herb Shields Rat Livers and Kidneys From Fluoride Damage

A humble tropical weed long used in traditional medicine across Africa and Asia may hold real protective power against one of the most widespread environmental contaminants on Earth. In a new laboratory study published in Discover Toxicology, researchers in Delta State, Nigeria, report that extracts of Phyllanthus amarus, a small annual herb of the Euphorbiaceae family, substantially reduced the liver and kidney damage caused by sodium fluoride in rats. The findings, drawn from careful biochemical measurements and tissue examinations, add to a growing body of evidence that polyphenol-rich plants can counteract the oxidative cascade that fluoride sets off inside the body. The work was carried out by Gabriel Otunuya Ibobo of Novena University, Joel Okpoghono of Delta State University of Science and Technology, and Innocent Onyesom of Delta State University, and was published as an open-access article in February 2025.

Fluoride occupies an unusual position in public health. Deliberately added to drinking water in controlled amounts to protect teeth, it also enters the environment through industrial processes ranging from phosphate fertilizer production to aluminum smelting, coal combustion, and the manufacture of glass, ceramics, and bricks. In regions with fluoride-rich minerals, well water can contain concentrations approaching 10 milligrams per liter, far above levels considered desirable. Food contributes as well: vegetables grown in contaminated fields, fish, and especially tea can carry appreciable fluoride loads, with dry tea leaves averaging around 100 milligrams per kilogram. Because the element is non-biodegradable, exposure is essentially continuous for many populations, making the search for practical protective strategies a matter of genuine urgency.

The biological problem with excess fluoride is that it behaves as a pro-oxidant. When fluoride intake overwhelms the body’s antioxidant defenses, free radicals accumulate faster than they can be neutralized, a state known as oxidative stress. This stress attacks the macromolecules of the cell, peroxidizing membrane lipids, damaging proteins, and breaking DNA strands. Previous studies in mice given sodium fluoride in drinking water showed depleted glutathione in the liver, along with DNA strand breaks, micronucleus formation, and the appearance of oxidized DNA adducts such as 8-hydroxy-2-deoxyguanosine. Such damage can push cells toward genotoxicity, somatic mutation, and apoptosis, the controlled self-destruction that follows irreparable injury. The liver, as the body’s principal detoxification organ, and the kidney, which receives roughly a fifth of cardiac output and concentrates circulating toxins, are particularly vulnerable targets.

To test whether Phyllanthus amarus could intervene, the team harvested leaves from Umuosele community in Amai, Nigeria, dried and powdered them, and extracted 500 grams of the material in methanol over 48 hours. The crude extract was then separated by liquid-liquid partitioning into fractions of differing polarity, using n-hexane, diethyl ether, n-butanol, methanol, and water. Yields varied considerably, with the methanol crude extract giving 37.62 percent, the methanol fraction 28.40 percent, and the aqueous fraction only 7.30 percent. The researchers selected the crude extract, the highest-yielding methanol fraction, and the lowest-yielding aqueous fraction for animal testing, dissolving each in 5 percent Tween 80 to a working concentration of 0.11 grams per milliliter.

Safety came first. In a preliminary lethal dose assessment involving sixty rats, no deaths occurred at oral doses from 100 to 1600 milligrams per kilogram of body weight across the fractions and crude extract. Rats receiving the higher doses showed reduced locomotion, but the 400 milligram per kilogram dose was well tolerated and even associated with normal hair growth, so the team adopted it for the main experiment. Thirty male Wistar rats, aged seven to nine weeks, were then divided into six groups of five. One group served as an untreated control, two groups received sodium fluoride alone or with the Tween 80 vehicle, and three groups received sodium fluoride alongside either the aqueous fraction, the methanol fraction, or the crude extract. Sodium fluoride was dosed orally at 25 milligrams per kilogram per day, and all treatments ran concurrently for 28 days before the animals were sacrificed and their tissues analyzed.

The results were striking. Rats exposed to sodium fluoride alone showed significant decreases in the activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase, along with depleted levels of reduced glutathione, in both liver and kidney tissue. At the same time, malondialdehyde, the standard chemical marker of lipid peroxidation and membrane damage, rose significantly. Histological examination confirmed the biochemical picture: livers of fluoride-exposed rats showed necrosis, while kidneys displayed detachment of the glomerulus from Bowman’s capsule, clear signs of structural injury consistent with fluoride-induced oxidative stress.

Co-treatment with Phyllanthus amarus reversed much of this damage. In the groups receiving the aqueous fraction, the methanol fraction, or the crude extract, glutathione levels and the activities of all four antioxidant enzymes rose significantly compared with the fluoride-only animals, while malondialdehyde concentrations fell. The authors attribute this rescue effect to the plant’s rich polyphenol content, which can scavenge free radicals and thereby preserve the metal-dependent antioxidant enzymes that fluoride disrupts. Superoxide dismutase converts the superoxide anion into hydrogen peroxide, which catalase and glutathione peroxidase then eliminate, while glutathione-S-transferase conjugates electrophilic toxins for excretion. By keeping this enzymatic chain intact, the extracts appear to have restored the oxidative balance that fluoride had tipped.

Perhaps the most consequential finding concerned DNA. Using a diphenylamine-based fragmentation assay, the researchers measured how much DNA in liver and kidney tissue had been broken into pieces, a sensitive indicator of genotoxic injury. Fluoride-exposed rats showed markedly elevated DNA fragmentation in both organs, but the three treatment groups showed significant reductions. Notably, the crude extract outperformed the methanol fraction, a difference the authors suggest reflects the higher concentration of bioactive compounds present in the unfractionated preparation. The team proposes that the plant’s antioxidants reduce the electrophilic chemicals that would otherwise attack DNA, preventing the multiple lesions that fluoride toxicity can produce.

The study is not without limitations, which the authors acknowledge candidly. Financial constraints prevented characterization of the specific active constituents in the crude extract and fractions, so the precise molecules responsible for the protective effect remain unidentified. The work was also conducted in a small number of animals over a single 28-day window, and findings in rats do not automatically translate to humans. Nevertheless, the researchers argue that Phyllanthus amarus leaves merit further investigation as an affordable and accessible alternative for managing renal and hepatic disorders linked to fluoride and other oxidative stressors, particularly in regions where fluoride contamination of water and food is endemic.

For a plant that traditional healers have long prescribed for ailments ranging from hepatitis and malaria to diarrhea and skin disease, the new data provide a mechanistic footing for at least one of its claimed benefits. If subsequent studies can identify the active compounds and confirm protective effects at realistic exposure levels, a weed that grows freely across the tropics could become a low-cost ally against an environmental toxin that no one can entirely avoid. For now, the message from the Nigerian laboratory is clear: in rats at least, the chemistry of Phyllanthus amarus stands between fluoride and the fragile DNA of the liver and kidney.

Subject of Research: Protective effects of Phyllanthus amarus extracts against sodium fluoride-induced oxidative stress and DNA damage in rat liver and kidney

Article Title: Impact of Phyllanthus amarus on fragmented DNA and antioxidant activity of rats exposed to sodium fluoride

Article References: Ibobo, G. O., Okpoghono, J., & Onyesom, I. (2025). Impact of Phyllanthus amarus on fragmented DNA and antioxidant activity of rats exposed to sodium fluoride. Discover Toxicology, 2(1), Article 2. https://doi.org/10.1007/s44339-025-00017-x

Image Credits: AI Generated

DOI: 10.1007/s44339-025-00017-x

Keywords: Phyllanthus amarus, sodium fluoride, oxidative stress, DNA fragmentation, antioxidant enzymes, lipid peroxidation, malondialdehyde, glutathione, hepatotoxicity, nephrotoxicity, polyphenols, toxicology