A 2026 Brazilian study followed 30 Bothrops snakebite patients for 48 hours after antivenom and found that mild cases gradually restored the molecular balance needed for tissue repair, while severe cases remained dysregulated, suggesting the body’s response may influence recovery

Snake venom does not necessarily stop causing tissue problems the moment antivenom is administered. A new study from researchers in Brazil suggests that the body's own response to the bite may play an important role in determining whether damaged tissue begins to recover or remains trapped in a prolonged inflammatory state.

The research, published April 24, 2026, in PLOS Neglected Tropical Diseases, examined the behavior of a group of enzymes called matrix metalloproteinases (MMPs) and their natural inhibitors, known as tissue inhibitors of metalloproteinases (TIMPs), in patients bitten by Bothrops snakes.

Bothrops snakes are responsible for a large proportion of snakebite envenomations in Brazil. Their venom can cause severe pain, swelling, bleeding and extensive local tissue damage.

Researchers followed 30 snakebite patients before and after antivenom

Led by Juliana Costa Ferreira Neves, the researchers prospectively followed 30 people with suspected Bothrops envenomation treated at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado in the Brazilian Amazon. The patients were divided into mild and severe cases according to their clinical symptoms. The study also included 20 healthy blood donors as a comparison group.

Blood samples were collected immediately before antivenom treatment and again 24 and 48 hours after treatment. The researchers measured five MMPs—MMP-1, MMP-2, MMP-7, MMP-9 and MMP-10—and four TIMPs—TIMP-1, TIMP-2, TIMP-3 and TIMP-4.

The goal was to see whether these molecules behaved differently in patients who developed mild versus severe disease.

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What are MMPs and TIMPs?

MMPs are enzymes that help break down components of the extracellular matrix, the structural network surrounding cells. This process is essential for normal tissue maintenance, inflammation and wound healing.

According to the National Cancer Institute, zinc or calcium is required for them to function, which is why they are called “metallo” proteinases. These enzymes help the body carry out normal tasks like healing wounds and growing new blood vessels, but they can also help cancer cells break through tissue barriers and spread to other parts of the body

But excessive or poorly controlled MMP activity can contribute to tissue destruction. TIMPs act as natural regulators of MMPs. Together, the two systems help maintain a balance between breaking down damaged tissue and rebuilding it.

The researchers therefore focused on whether this MMP-TIMP balance changed as patients recovered from snakebite.

Severe bites showed a more disrupted molecular response

Before antivenom was administered, both mild and severe patients showed evidence of an activated MMP-TIMP system. MMP-1, MMP-7 and MMP-10 were significantly higher in snakebite patients than in healthy controls, while MMP-9 was lower. All four TIMPs measured in the study were also elevated in the envenomed patients.

However, the researchers found differences when comparing the patients. At the initial time point, severe cases had significantly higher levels of MMP-7, MMP-9, TIMP-1, TIMP-2 and TIMP-3 than mild cases, indicating a stronger and more disrupted early response.

The researchers then observed how these molecules changed after antivenom treatment.

Mild cases appeared to regain molecular balance

The biggest difference emerged during follow-up. In patients with mild envenomation, several MMPs and TIMPs changed after treatment in a pattern the researchers interpreted as a return toward a more regulated state. Some inflammatory and tissue-remodeling signals declined, while other MMPs involved in extracellular-matrix turnover remained active.

In severe cases, however, the molecular response remained more disrupted. The study found persistent changes in MMPs and TIMPs, which the researchers said could interfere with normal extracellular matrix reorganization and tissue repair.

This matters because antivenom neutralizes venom components, but it does not necessarily reverse tissue damage that has already occurred. Once the inflammatory and tissue-remodeling processes have been activated, they may continue even after the venom itself has been neutralized.

Delayed antivenom was also linked with more severe disease

The researchers found another important clinical difference: the severe group received antivenom later. Patients with mild envenomation received treatment after a median of 3 hours, while those in the severe group received it after a median of 6 hours.

The study found a strong association between delayed antivenom administration and greater clinical severity. However, because this was a relatively small observational study, the researchers cannot, from these findings alone, establish that treatment delay directly caused the more severe molecular response.

The consequences were visible in hospital stays as well. About 93% of mild cases were discharged within one to two days, while all severe cases required longer hospitalization, generally lasting three to five days.

Why the findings could matter

The study suggests that snakebite severity may not depend only on the amount or effects of venom itself. The body's subsequent inflammatory and tissue-remodeling response could also influence how well damaged tissue recovers.

The researchers propose that monitoring MMPs and TIMPs could eventually help identify patients at greater risk of complications or provide clues for treatments aimed at limiting tissue damage.

But that possibility remains preliminary. The study involved only 30 snakebite patients, and the researchers describe their molecular and network analyses as exploratory and hypothesis-generating. They also measured circulating MMPs and TIMPs rather than directly examining what was happening inside the damaged tissue.

Larger studies will therefore be needed to determine whether these molecular patterns can reliably predict which snakebite patients will develop severe tissue damage and whether targeting the MMP-TIMP system could actually improve recovery.

For now, the findings add another layer to the understanding of snakebite injury: the damage caused by venom may be followed by a prolonged battle inside the body between molecules that break down tissue and those that attempt to control the process and support repair.